Detection of egg white allergy in children by specific IgE microarray chemiluminescence immunoassay.

BACKGROUND: Allergen testing has emerged as a pivotal component in prevention and treatment strategies for allergic diseases among children and the utilization of specific IgE (sIgE) through a fully automated chemiluminescent microarray immunoassay (CLMIA) has emerged as a promising trend in the simultaneous detection of multiple allergenic components of children. METHODS: The accuracy and reliability of CLMIA were verified using children's serum samples that concentrated on allergens. the allergens. The clinical diagnostic practicability of CLMIA was assessed through comprehensive evaluations including measurements of the limit of detection (LOD), intra-batch, and inter-batch precision, linearity analysis, the cross-contamination rate, and the concordance rate with the Phadia system. RESULTS: After the optimization process of CLMIA, the LODs for allergens were calculated to be below 0.01 kU/L, demonstrating the high sensitivity of CLMIA. All components exhibited good linearity within the range of 0.1-100.0 kU/L and the coefficient of determinations (R2 > 0.99). The data of intra-batch precision (<10 %) and inter-batch data (<15 %) illustrated the high reproducibility of CLMIA. The cross-contamination rates for allergens (<0.5 %) showed the high accuracy of CLMIA without interfering. The positive concordance rate between CLMIA and the Phadia system exceeds 90 % with a good negative concordance rate (>85 %) and the Kappa coefficients (>0.8), suggesting the close alignment of CLMIA and the Phadia system and showing the satisfactory clinical potential of CLMIA in children's allergy disease. CONCLUSIONS: The application of CLMIA has been promising in allergen testing, especially for detecting multiple allergenic components in children.

Analysis of optical properties and response mechanism of H2S fluorescent probe based on rhodamine derivatives.

H2S plays a crucial role in numerous physiological and pathological processes. In this project, a new fluorescent probe, SG-H2S, for the detection of H2S, was developed by introducing the recognition group 2,4-dinitrophenyl ether. The combination of rhodamine derivatives can produce both colorimetric reactions and fluorescence reactions. Compared with the current H2S probes, the main advantages of SG-H2S are its wide pH range (5-9), fast response (30 min), and high selectivity in competitive species (including biological mercaptan). The probe SG-H2S has low cytotoxicity and has been successfully applied to imaging in MCF-7 cells, HeLa cells, and BALB/c nude mice. We hope that SG-H2S will provide a vital method for the field of biology.

Multifunctional fluorescence/photoacoustic bimodal imaging of γ-glutamyltranspeptidase in liver disorders under different triggering conditions.

Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.

Recurrent stroke shortly after mechanical thrombectomy secondary to carotid web: A case report.

RATIONALE: Carotid web, a known source of thrombus for embolic stroke, presents a considerable risk of stroke recurrence. While case reports have demonstrated the safety and effectiveness of mechanical thrombectomy in treating carotid web-related stroke, the need for concurrent carotid artery stenting to prevent recurrent stroke immediately after thrombectomy remains unclear. This study aims to underscore the importance of immediate carotid artery stenting in preventing recurrent stroke following mechanical thrombectomy in patients with carotid web-related stroke. PATIENT CONCERNS: A 43-year-old woman with acute onset of left limb weakness and slurred speech within 3 hours was admitted to the emergency department. DIAGNOSES: Computed tomographic angiography confirmed the M1 segment occlusion of the right middle cerebral artery. INTERVENTIONS: The patient received intravenous thrombolysis in the local hospital and mechanical thrombectomy in our stroke center. OUTCOMES: Three days post-mechanical thrombectomy, there was a sudden exacerbation of her neurological deficit symptoms. A reexamination via computed tomographic angiography revealed a re-occlusion in M1 segment of the right middle cerebral artery, despite the implementation of stringent anticoagulation therapy for carotid web-related stroke. LESSONS: Stroke patients with carotid web had a high risk of stroke recurrence and it was necessary to conduct carotid artery stenting to prevent stroke recurrence secondary to the carotid web immediately after mechanical thrombectomy.

An integrated PK/PD model investigating the impact of tumor size and systemic safety on animal survival in SW1990 pancreatic cancer xenograft.

Survival is one of the most important endpoints in cancer therapy, and parametric survival analysis could comprehensively reveal the overall result of disease progression, drug efficacy, toxicity as well as their interactions. In this study we investigated the efficacy and toxicity of dexamethasone (DEX) combined with gemcitabine (GEM) in pancreatic cancer xenograft. Nude mice bearing SW1990 pancreatic cancer cells derived tumor were treated with DEX (4 mg/kg, i.g.) and GEM (15 mg/kg, i.v.) alone or in combination repeatedly (QD, Q3D, Q7D) until the death of animal or the end of study. Tumor volumes and net body weight (NBW) were assessed every other day. Taking NBW as a systemic safety indicator, an integrated pharmacokinetic/pharmacodynamic (PK/PD) model was developed to quantitatively describe the impact of tumor size and systemic safety on animal survival. The PK/PD models with time course data for tumor size and NBW were established, respectively, in a sequential manner; a parametric time-to-event (TTE) model was also developed based on the longitudinal PK/PD models to describe the survival results of the SW1990 tumor-bearing mice. These models were evaluated and externally validated. Only the mice with good tumor growth inhibition and relatively stable NBW had an improved survival result after DEX and GEM combination therapy, and the simulations based on the parametric TTE model showed that NBW played more important role in animals' survival compared with tumor size. The established model in this study demonstrates that tumor size was not always the most important reason for cancer-related death, and parametric survival analysis together with safety issues was also important in the evaluation of oncology therapies in preclinical studies.

Structural basis for 18-ß-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor.

AIM: Glyoxalase I (GLOI), a glutathione (GSH)-dependent enzyme, is overexpressed in tumor cells and related to multi-drug resistance in chemotherapy, making GLOI inhibitors as potential anti-tumor agents. But the most studied GSH analogs exhibit poor pharmacokinetic properties. The aim of this study was to discover novel non-GSH analog GLOI inhibitors and analyze their binding mechanisms. METHODS: Mouse GLOI (mGLOI) was expressed in BL21 (DE3) pLysS after induction with isopropyl-ß-D-1-thiogalactopyranoside and purified using AKTA FPLC system. An in vitro mGLOI enzyme assay was used to screen a small pool of compounds containing carboxyl groups. Crystal structure of the mGLOI-inhibitor complex was determined at 2.3 Å resolution. Molecular docking study was performed using Discovery Studio 2.5 software package. RESULTS: A natural compound 18-ß-glycyrrhetinic acid (GA) and its derivative carbenoxolone were identified as potent competitive non-GSH analog mGLOI inhibitors with Ki values of 0.29 µmol/L and 0.93 µmol/L, respectively. Four pentacyclic triterpenes (ursolic acid, oleanolic acid, betulic acid and tripterine) showed weak activities (mGLOI inhibition ratio <25% at 10 µmol/L) and other three (maslinic acid, corosolic acid and madecassic acid) were inactive. The crystal structure of the mGLOI-GA complex showed that the carboxyl group of GA mimicked the γ-glutamyl residue of GSH by hydrogen bonding to the glutamyl sites (residues Arg38B, Asn104B and Arg123A) in the GSH binding site of mGLOI. The extensive van der Waals interactions between GA and the surrounding residues also contributed greatly to the binding of GA and mGLOI. CONCLUSION: This work demonstrates a carboxyl group to be an important functional feature of non-GSH analog GLOI inhibitors.

Profiling of glucosinolates and flavonoids in Rorippa indica (Linn.) Hiern. (Cruciferae) by UHPLC-PDA-ESI/HRMS(n).

An UHPLC-PDA-ESI/HRMS(n) profiling method was used to identify the glucosinolates and flavonoids of Rorippa indica (Cruciferae), a wild vegetable and Chinese herb used to treat cough, diarrhea, and rheumatoid arthritis. Thirty-three glucosinolates, more than 40 flavonol glycosides, and 18 other phenolic and common organic compounds were identified. The glucosinolates and polyphenols were separated by UHPLC. High-resolution deprotonated molecules provided high accuracy mass values that were used to determine formulas and provide putative identification of the glucosinolates and flavonoids. The fragments from multistage mass spectrometry were used to elucidate the structures. The concentrations of the main components were based on UV peak areas and molar relative response factors with a single calibration standard. This study found this plant to be a rich source for glucosinolates, containing 24 new glucosinolates, including 14 glucosylated glucosinolates that were previously unidentified.

Rhodium-catalyzed chemo- and regioselective cross-dimerization of two terminal alkynes.

Cross-dimerization of terminal arylacetylenes and terminal propargylic alcohols/amides has been achieved in the presence of a rhodium catalyst. This method features high chemo- and regioselectivities rendering convenient and atom economical access to functionalized enynes.

Quantitation of the hydroxycinnamic acid derivatives and the glycosides of flavonols and flavones by UV absorbance after identification by LC-MS.

A general approach was developed to quantify hydroxycinnamic acid derivatives and the glycosides of flavonols and flavones using UV molar relative response factors (MRRFs). More than 90 standards were analyzed by LC-MS and divided into five groups based on the λ(max) of their band I absorbance profiles. For each group, a commercially available standard was chosen as the group reference standard. Response factors were determined for each standard in each group as purchased (MRRF) and, when possible, after vacuum drying (MRRF(D)). The MRRF(D) values for 17 compounds whose λ(max) values fell within ±2 nm of the group reference standard were 1.01 ± 0.03. MRRF values for compounds whose λ(max) values fell within ±10 nm of the group reference standard were 0.96 ± 0.13. Group reference standards were used to quantify 44 compounds in Chinese lettuce, red onion, and white tea. This approach allows quantitation of numerous compounds for which there are no standards.