Strategies for the Immobilization and Signal Amplification of a Double Nanobody Sandwich ELISA for Human Microsomal Epoxide Hydrolase.

The microsomal epoxide hydrolase (mEH) is important in the detoxification of carcinogens in the liver and other tissues but is also a blood biomarker of hepatitis and liver cancer. Improved analytical methods are needed for the study of its role in the metabolism of xenobiotics and endogenous roles as a blood biomarker of diseases. The development of a double nanobody sandwich ELISA offers significant improvements over traditional polyclonal or monoclonal antibody-based assays, enhancing both the homogeneity and the stability of assay production.

-Active Soluble Epoxide Hydrolase-Targeting PROTACs with Improved Potency and Stability.

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme involved in fatty acid metabolism and a promising drug target. We previously reported first-generation sEH proteolysis-targeting chimeras (PROTACs) with limited degradation potency and low aqueous and metabolic stability. Herein, we report the development of next-generation sEH PROTAC molecules with improved stability and degradation potency.

Metabolomics reveals soluble epoxide hydrolase as a therapeutic target for high-sucrose diet-mediated gut barrier dysfunction.

Highsucrose diet (HSD) was reported as a causative factor for multiorgan injuries. The underlying mechanisms and therapeutic strategies remain largely uncharted. In the present study, by using a metabolomics approach, we identified the soluble epoxide hydrolase (sEH) as a therapeutic target for HSD-mediated gut barrier dysfunction.

Fabrication of a high-sensitivity electrochemical immunosensor by the oriented immobilization of engineered nanobody on nanofibrous membrane.

A new type of label-free electrochemical immunosensor for the high-sensitivity determination of parathion was developed based on the oriented immobilization of nanobody (VHH9) on a gold nanoparticle-loaded polyvinyl alcohol/citric acid nanofiber membrane-modified electrode. The morphology characterization and assembly process of the modified materials were investigated using scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). Under the optimum conditions, the label-free electrochemical immunosensor for parathion exhibited a linear range of 0.

Differential lipid signaling from CD4 and CD8 T cells contributes to type 1 diabetes development.

Introduction: We reported that Ca-independent phospholipase Aβ (iPLAβ)-derived lipids (iDLs) contribute to type 1 diabetes (T1D) onset. As CD4 and CD8 T cells are critical in promoting β-cell death, we tested the hypothesis that iDL signaling from these cells participates in T1D development.

Methods: CD4 and CD8 T cells from wild-type non-obese diabetic () and .

Soluble epoxide hydrolase inhibition impairs triggering receptor expressed on myeloid cells-1 in periodontal tissue.

Aims: Periodontitis is a prevalent inflammatory disorder affecting the oral cavity, driven by dysbiotic oral biofilm and host immune response interactions. While the major clinical focus of periodontitis treatment is currently controlling oral biofilm, understanding the immune response is crucial to prevent disease progression. Soluble epoxide hydrolase (sEH) inhibition has shown promise in preventing alveolar bone resorption.

Randomized, double-blind, phase 1a single-ascending dose and food effect studies assessing safety and pharmacokinetics of EC5026 in healthy volunteers.

Chronic pain represents a significant unmet medical need, affecting one-fifth of the U.S. population.

Inhibition of Soluble Epoxide Hydrolase Ameliorates Cerebral Blood Flow Autoregulation and Cognition in Alzheimer's Disease and Diabetes-Related Dementia Rat Models.

Alzheimer's Disease and Alzheimer's Disease-related dementias (AD/ADRD) pose major global healthcare challenges, with diabetes mellitus (DM) being a key risk factor. Both AD and DM-related ADRD are characterized by reduced cerebral blood flow, although the exact mechanisms remain unclear. We previously identified compromised cerebral hemodynamics as early signs in TgF344-AD and type 2 DM-ADRD (T2DN) rat models.

4-Phenyl-thiazole-based dual inhibitors of fatty acid amide hydrolase and soluble epoxide hydrolase do not alleviate orofacial inflammatory pain in female rats.

Pain arising from trigeminal systems such as headache is common, debilitating, and current treatments (e.g., sumatriptan) are limited.

Urinary metabolic profile and its predictive indexes after MSG consumption in rat.

Monosodium glutamate (MSG) is a widely used food additive with conflicting evidence regarding its potential effects on human health, with proposed relevance for obesity and metabolic syndrome (MetS) or chronic kidney disease. As being able to accurately quantify the MSG dietary intake would help clarify the open issues, we constructed a predictive formula to estimate the daily intake of MSG in a rat model based on the urinary metabolic profile. Adult male Wistar rats were divided into groups receiving different daily amounts of MSG in drinking water (0.

-Active Soluble Epoxide Hydrolase-targeting PROTACs with Improved Potency and Stability.

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme involved in fatty acid metabolism and promising drug target. We previously reported first-generation sEH proteolysis-targeting chimeras (PROTACs) with limited degradation potency and low aqueous and metabolic stability. Herein, we report the development of next-generation sEH PROTAC molecules with improved stability and degradation potency.

Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain.

Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund's adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound (1,1'-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models.

Triazine herbicide prometryn alters epoxide hydrolase activity and increases cytochrome P450 metabolites in murine livers via lipidomic profiling.

Oxylipins are a group of bioactive fatty acid metabolites generated via enzymatic oxygenation. They are notably involved in inflammation, pain, vascular tone, hemostasis, thrombosis, immunity, and coagulation. Oxylipins have become the focus of therapeutic intervention since they are implicated in many conditions, such as nonalcoholic fatty liver disease, cardiovascular disease, and aging.

Versatility and stability of melamine foam-based biosensors (f-ELISA) using antibodies, nanobodies, and peptides as sensing probes.

Macroporous three-dimensional (3D) framework structured melamine foam-based Enzyme-Linked Immunosorbent Assay (f-ELISA) biosensors were developed for rapid, reliable, sensitive, and on-site detection of trace amount of biomolecules and chemicals. Various ligands can be chemically immobilized onto the melamine foam, which brings in the possibility of working with antibodies, nanobodies, and peptides, respectively, as affinity probes for f-ELISA biosensors with improved stability. Different chemical reagents can be used to modify the foam materials, resulting in varied reactivities with antibodies, nanobodies, and peptides.

Evaluation of the Immune Response of Patulin by Proteomics.

Patulin, an emerging mycotoxin with high toxicity, poses great risks to public health. Considering the poor antibody production in patulin immunization, this study focuses on the four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics to reveal the immune response of patulin in rabbits. The rabbit immunization was performed with the complete developed antigens of patulin, followed by the identification of the immune serum.

Shark anti-idiotypic variable new antigen receptor specific for an alpaca nanobody: Exploration of a nontoxic substitute to ochratoxin A in immunoassay.

Nontoxic substitutes to mycotoxins can facilitate the development of eco-friendly immunoassays. To explore a novel nontoxic substitute to ochratoxin A (OTA), this study screened shark anti-idiotypic variable new antigen receptors (VNARs) against the alpaca anti-OTA nanobody Nb28 through phage display. After four rounds of biopanning of a naïve VNAR phage display library derived from six adult Chiloscyllium plagiosum sharks, one positive clone, namely, P-3, was validated through a phage enzyme-linked immunosorbent assay (phage ELISA).

Correction: Novel aerosol treatment of airway hyper-reactivity and inflammation in a murine model of asthma with a soluble epoxide hydrolase inhibitor.

[This corrects the article DOI: 10.1371/journal.pone.

Quinolinyl-based multitarget-directed ligands with soluble epoxide hydrolase and fatty acid amide hydrolase inhibitory activities: Synthetic studies and pharmacological evaluations.

Simultaneous inhibition of soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH) with a single small molecule represents a novel therapeutic approach in treating inflammatory pain, since both targets are involved in pain and inflammation processes. In this study using multi-target directed ligands methodology we designed and synthesized 7 quinolinyl-based dual sEH/FAAH inhibitors, using an optimized microwave-assisted Suzuki-Miyaura coupling reaction and tested their potency in human FAAH and human, rat, and mouse sEH inhibition assays. The structure-activity relationship study showed that quinolinyl moiety is well tolerated in the active sites of both enzymes, yielding several very potent dual sEH/FAAH inhibitors with the IC values in the low nanomolar range.

A new strategy to generate nanobodies for the coumaphos based on the synthesized nanobody libraries.

To break through the bottleneck in preparation of nanobody (Nb) for chemical contaminants induced by the difficulties in the synthesis of immunogen, complexity and unexpectable efficiency of immunization, a novel strategy to generate Nbs based on the designed synthetic Nb libraries with final size up to 10 cfu/mL was adopted and succeeded in selection of anti-coumaphos Nb A4. Furthermore, an affinity-matured mutant Nb 3G was obtained from the secondary library. Finally, an ic-ELISA was established with the limit of detection for coumaphos low to 1.

Effects of sEH inhibition on the eicosanoid and cytokine storms in SARS-CoV-2-infected mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves an initial viral infection phase followed by a host-response phase that includes an eicosanoid and cytokine storm, lung inflammation and respiratory failure. While vaccination and early anti-viral therapies are effective in preventing or limiting the pathogenic host response, this latter phase is poorly understood with no highly effective treatment options. Inhibitors of soluble epoxide hydrolase (sEH) increase levels of anti-inflammatory molecules called epoxyeicosatrienoic acids (EETs).

Fluorescent and Colorimetric Dual-Readout Immunochromatographic Assay for the Detection of Phenamacril Residues in Agricultural Products.

The fungicide phenamacril has been employed to manage and mycotoxins in crops, leading to persistent residues in the environment and plants. Detecting phenamacril is pivotal for ensuring environmental and food safety. In this study, haptens and artificial antigens were synthesized to produce antiphenamacril monoclonal antibodies (mAbs).