Development of Highly Sensitive Immunochromatography Using Time-Resolved Fluorescence Microspheres for Amantadine Detection.

Amantadine (AMA), commonly used to treat viral infections in livestock and poultry, has been banned owing to its potential hazards to human well-being. To detect unauthorized AMA usage in livestock, we developed a polyclonal antibody with a high affinity for the specific recognition of AMA through a rational design based on a structure similar to AMA and revealed the availability of the hapten design by computational chemistry analysis. Using this antibody, we established a highly responsive time-resolved fluorescence immunochromatographic assay (TRFICA).

Design, synthesis and bioactivity evaluation of isobavachin derivatives as hURAT1 inhibitors for hyperuricemia agents.

Previously, we reported a novel natural scaffold compound, isobavachin (4',7-dihydroxy-8-prenylflavanone), as a highly potent hURAT1 inhibitor with anti-hyperuricemia effect. However, the structure-activity relationship remains unknown and the poor pharmacokinetic (PK) parameters may limit further clinical use. Herein, a series of isobavachin derivatives were rationally designed and synthesized to explore the structure-activity relationship of isobavachin target hURAT1, and to improve their PK properties.

Development of a monoclonal antibody-based time-resolved fluorescence immunochromatographic assay strip for sensitively detecting florfenicol residues in milk and eggs: Theoretical chemical insights into unexpected high specificity.

Florfenicol (FF), with its broad-spectrum antibacterial activity, is frequently abused in the livestock and poultry industries and has aroused the growing public concern. Owing to structural similarities and varying maximum residue limits between florfenicol and other chloramphenicol (CAP)-type antibiotics, including thiamphenicol (TAP) and chloramphenicol (CAP), there is an urgent need for a rapid and effective immunoassay method to distinguish them, in order to minimize the risk of false positives. Fortunately, a highly specific monoclonal antibody (mAb), named as SF11, has been developed using hybridoma technology.

Discovery of digallic acid as XOD/URAT1 dual target inhibitor for the treatment of hyperuricemia.

The development of XOD/URAT1 dual target inhibitors has emerged as a promising therapeutic strategy for the management of hyperuricemia. Here, through virtual screening, we have identified digallic acid as a novel dual target inhibitor of XOD/URAT1 and subsequently evaluated its pharmacological properties, pharmacokinetics, and toxicities. Digallic acid inhibited URAT1 with an IC of 5.

Designing a size exclusion-based hapten and the development of a quantitative and visual time-resolved fluorescence immunochromatography assay strip for detecting dimethomorph and flumorph in a group-specific manner.

Based on the size and surface properties of dimethomorph and flumorph, we used a computer simulation-assisted size exclusion hapten design strategy to develop group-specific monoclonal antibodies that can simultaneously recognize dimethomorph and flumorph. For this, we performed quantitative and visual semi-quantitative time-resolved fluorescence immunochromatography (TRFICA) to simultaneously detect dimethomorph and flumorph in potatoes and apples. In potato samples, the visual limit of detection (vLOD) for dimethomorph and flumorph was 4 ng/mL and 8 ng/mL, respectively, whereas the quantitative limit of detection (qLOD) for dimethomorph and flumorph was 0.

Development of an Open Droplet Microchannel-Based Magnetosensor for Immunofluorometric Assay of Trimethoprim in Chicken and Pork Samples with a Wide Linear Range.

Trimethoprim (TMP), functioning as a synergistic antibacterial agent, is utilized in diagnosing and treating diseases affecting livestock and poultry. Human consumption of the medication indirectly may lead to its drug accumulation in the body and increase drug resistance due to its prolonged metabolic duration in livestock and poultry, presenting significant health hazards. Most reported immunoassay techniques, such as ELISA and immunochromatographic assay (ICA), find it challenging to achieve the dual advantages of high sensitivity, simplicity of operation, and a wide detection range.

Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1 and ALK.

Clinical treatment by FDA-approved ROS1/ALK inhibitor Crizotinib significantly improved the therapeutic outcomes. However, the emergence of drug resistance, especially driven by acquired mutations, have become an inevitable problem and worsened the clinical effects of Crizotinib. To combat drug resistance, some novel 2-aminopyridine derivatives were designed rationally based on molecular simulation, then synthesised and subjected to biological test.

B13, a well-tolerated inhibitor of hedgehog pathway, exhibited potent anti-tumor effects against colorectal carcinoma in vitro and in vivo.

Abnormal activation of Hedgehog (Hh) signaling pathway mediates the genesis and progression of various tumors [1]. Currently, three drugs targeting the Hh signaling component Smoothened (Smo) have been marketed for the clinical treatment of basal cell tumors or acute myeloid leukemia. However, drug resistance is a common problem in those drugs, so the study of Smo inhibitors that can overcome drug resistance has important guiding significance for clinical adjuvant drugs.

Pharmacological evaluation of a novel skeleton compound isobavachin (4',7-dihydroxy-8-prenylflavanone) as a hypouricemic agent: Dual actions of URAT1/GLUT9 and xanthine oxidase inhibitory activity.

Previously we discovered a novel natural scaffold compound, isobavachin (4', 7-dihydroxy-8-prenylflavanone), as a potent URAT1 inhibitor by shape and structure based on a virtue screening approach. In this study, further urate-lowering mechanism, pharmacokinetics and toxicities of isobavachin were conducted. Isobavachin inhibited URAT1 with an IC value of 0.

Mutation in Transmembrane Domain 8 of Human Urate Transporter 1 Disrupts Uric Acid Recognition and Transport.

Human urate transporter 1 (hURAT1) is the most pivotal therapeutic target for hyperuricemia. Due to a lack of crystal structure information, the atomic structure of URAT1 is not clearly understood. In this study, a multiple sequence alignment was performed, and K393, a positively charged residue in transmembrane domain (TMD) 8, was observed to be highly conserved in organic anion transporters (OATs).

Ultrasensitive and rapid colorimetric detection of paraquat via a high specific VHH nanobody.

Rapid and quantitative detection of paraquat is crucial because of its high toxicity. Here, we developed an ultrasensitive time-resolved fluorescence immunochromatographic assay (TRFICA) strip based on our synthesized variable domain of heavy chain antibody (VHH, also called Nanobody) for paraquat detection. Briefly, the specific immunogen selected from six designed antigens was employed to immunize alpaca, and a high-efficiency capacity of 1.

Improved molecular softness of tadalafil hapten enhancing antibody performance in immunoassay: Evidence from computational chemistry.

The tadalafil-like compounds have appeared recently as adulterants in drinks and healthcare dietary supplements sourced from medicinal and edible food, which may cause illness and even death. In this work, the rationality of haptens was explored by computational chemistry and molecular simulation theories such as frontier molecular orbital (FMO)-based softness (S), three-dimensional (3D) structure, surface electrostatic potential (ESP), and lipophilic potential (LP). An antiserum from hapten H5 with the highest softness and maintaining the appropriate three-dimensional (3D) structure showed the optimal immunoassay performance, indicating an increasing softness was a critical factor for effective hapten.

The gut microbial metabolite, 3,4-dihydroxyphenylpropionic acid, alleviates hepatic ischemia/reperfusion injury mitigation of macrophage pro-inflammatory activity in mice.

Hepatic ischemia/reperfusion injury (HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI.

Novel natural scaffold as hURAT1 inhibitor identified by 3D-shape-based, docking-based virtual screening approach and biological evaluation.

As a promising therapeutic target for gout, hURAT1 has attracted increasing attention. In this work, we identified a novel scaffold of hURAT1 inhibitors from a personal natural product database of verified herb-treated gout. First, we constructed more than 800 natural compounds from Chinese medicine that were verified to treat gout.

Development of Time-Resolved Fluorescence Immunochromatographic Assays for Simultaneously Detecting Tylosin and Tilmicosin in Milk in Group-Screening Manner.

Tylosin and tilmicosin (T&T) residues in livestock products have received extensive attention from consumers. Time-resolved fluorescence immunochromatographic assay (TRFICA), as a fast, efficient and sensitive immunoassay method, has played an increasingly important role in the food safety field. Therefore, herein a quantitative and visual TRFICA was established for simultaneously detecting T&T in milk in a group-screening manner.

Development of a group-specific antibody-based immunoassay method for simultaneously detecting sildenafil-like adulterants in herbal spirit drinks.

Phosphodiesterase type 5 (PDE-5) inhibitors are commonly used to treat erectile dysfunction. There is a problem with synthesis and illegal use of a wide range of analogues of the licenced drugs and a simple class-wide analytical method is required. In this work, based on structural modelling, we developed an immunological method using norneovardenafil as a hapten as it contains only the general sub-structure and the common features of sildenafil-like adulterants, such as hydrophobic centres, hydrogen-bond donor atoms and hydrogen-bond acceptor atoms.

CDER167, a dual inhibitor of URAT1 and GLUT9, is a novel and potent uricosuric candidate for the treatment of hyperuricemia.

Urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) are important targets for the development of uric acid-lowering drugs. We previously showed that the flexible linkers of URAT1 inhibitors could enhance their potency. In this study we designed and synthesized CDER167, a novel RDEA3710 analogue, by introducing a linker (methylene) between the naphthalene and pyridine rings to increase flexibility, and characterized its pharmacological and pharmacokinetics properties in vitro and in vivo.

Multiple modes of action of myricetin in influenza A virus infection.

Influenza A virus remains a major threat to public health worldwide after its first pandemic. Scientists keep searching novel anti-influenza drugs, of which natural products present to be an important source. Myricetin, a natural flavonol compound, which exists in many edible plants, which has a wide range of biological activities, but its anti-influenza A virus activity is ambiguous.

Structural Insights into the Atomistic Mechanisms of Uric Acid Recognition and Translocation of Human Urate Anion Transporter 1.

: Human urate transporter 1 (hURAT1) is the most pivotal therapeutic target for treating hyperuricemia. However, the molecular interactions between uric acid and URAT1 are still unknown due to lack of structural details. : In the present study, several methods (homology modeling, sequence alignment, docking, and mutagenesis) were used to explain the atomistic mechanisms of uric acid transport of hURAT1.

A gold nanoparticle-based immunochromatographic assay for simultaneous detection of multiplex sildenafil adulterants in health food by only one antibody.

In the last few years, sildenafil and its analogues have emerged as an illegal ingredient in health food and products, causing illness and death. To address this problem, herein, a gold nanoparticle-based immunochromatographic assay for simultaneous detection sildenafil and its analogues was developed by using just one monoclonal antibody. This method can realize qualitative and quantitative analysis of sildenafil and its analogues with a detection range (IC-IC) of 0.