Oglufanide disodium

The leading factors in the pathogenesis of chronic polyposis rhinosinusitis (CRSwNP) are dysfunction of the epithelial barrier of the nasal and sinus mucosa and dysregulation of the immune system, both at the systemic and local levels. A Th2-mediated immune response plays a central role in the development of disease in patients with CRSwNP CRPS, and CRSwNP is often associated with bronchial asthma (BA). At the present time, for the conservative treatment of patients with CRSwNP+BA, preference is given to drug therapy aimed at the correction of mucosal immunity. The use of interferon α2β (IFN α2β) and the dipeptide γ-D-glutamyl-L-tryptophan may reduce the severity of the long-term local inflammatory process. However, the clinical efficacy of these drugs in the context of chronic polyposis has not been studied. The aim of this study was to compare the efficacy of topical application of recombinant IFN α2β, recombinant IFN α2β in combination with γ-D-glutamyl-L-tryptophan and IL-4Rα receptor inhibitor in the treatment of patients with CRSwNP+BA. The patients were divided into three groups. In the first group (31 people), 1 million units of interferon alpha2b were injected into the polyposis tissue for five days. In the second group (31 people), interferon alpha2b at a dose of 1 million units and gamma-D-glutamyl-L-tryptophan at a dose of 0.1 mg were injected into the polypous tissue for five days. To assess the dynamics of clinical symptoms in the reference group (31 people), a drug with a known mechanism of action and efficacy — a genetically engineered IL-4Rα receptor inhibitor — was used. This drug was used 300 mg once every 2 weeks subcutaneously for 1 year. The obtained results showed that recombinant IFN α2β in combination with γ-D-glutamyl-L-tryptophan are pathogenetically appropriate preparations for conservative treatment of patients with the following initial indicators: severity of the polyposis process — 2.2+0.2 points, swelling — 2.8+0.4 points, and amount of discharge — 2.9+0.3 points. A single 5-day course of the above-mentioned preparations had a positive therapeutic effect, which was accompanied by a pronounced reduction in the clinical symptoms of the disease: the volume of polyposis tissue, nasal breathing difficulties and swelling of the nasal mucosa after one month and was maintained for one year. At the same time, the results of our study indicate the necessity of a longer period of application of recombinant IFN α2β in combination with γ-D-glutamyl-L-tryptophan in patients with CRSwNP+BA. The data obtained were comparable to the corresponding indicators when using the IL-4Ra inhibitor. In our opinion, the mechanism of action of the preparations is associated with a decrease in the activity of inflammatory and proliferative processes in the nasal and sinus mucosa.

Tissue metabolomics analysis, alongside genomics and proteomics, offers crucial insights into the regulatory mechanisms of tumorigenesis. To enhance metabolite detection sensitivity, chemical isotope labeling (CIL) techniques, such as dansylation, have been developed to improve metabolite separation and ionization in mass spectrometry (MS). However, the dissolution of hydrophobic derivatized metabolites in solvents with high acetonitrile content limits the use of liquid chromatography (LC) systems with small-volume reversed-phase (RP) columns. In this study, we established a nano-LC-MS system with an online dilution design to address this issue, enabling sensitive analysis of oral cancer tissue metabolomes.

Our nano-LC system features a flow path design with online sample dilution before an RP trap column and backflushing of the trap column before entering the analytical column. Compared to other nano-LC systems, both with and without online dilution designs, our system demonstrates the superiority of the T-connector-based dilution method. Using only 1/20th of the sample required for popular micro-LC systems, our nano-LC detects a larger number of peak pairs with similar recovery rates for both hydrophilic and hydrophobic metabolites, ensuring unbiased results. Thirty-two matched pairs of oral squamous cell carcinoma (OSCC) tissue samples and adjacent noncancerous tissues (ANTs) underwent high-throughput CIL-metabolome analysis using our nano-LC system. Compared to our previous micro-LC methods, the nano-LC-MS system exhibits enhanced detection sensitivity, significantly reducing sample requirements.

Our findings highlight the efficacy of our platform for metabolomic analysis with limited sample amounts. The nano-LC system's ability to analyze samples dissolved in strong eluents suggests potential applications for handling other hydrophobic compounds using RPLC or other separation methods facing similar solvent incompatibility issues. This approach holds promise for identifying novel metabolite biomarkers for oral cancers, advancing our understanding of tumorigenesis, and enhancing clinical applications.