Exhaled breath analysis in adult patients with cystic fibrosis by real-time proton mass spectrometry.

BACKGROUND: Proton-transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) is a promising tool for a rapid online determination of exhaled volatile organic compounds (eVOCs) profiles in patients with cystic fibrosis (CF). OBJECTIVE: To detect VOC breath signatures specific to adult patients with CF compared with controls using PTR-TOF-MS. METHODS: 102 CF patients (54 M/48, mean age 25.6 ± 7.8 yrs) and 97 healthy controls (56 M/41F, mean age 25.8 ± 6.0 yrs) were examined. Samples from normal quiet breathing and forced expiratory maneuvers were analyzed with PTR-TOF-MS (Ionicon, Austria) to obtain VOC profiles listed as ions at various mass-to-charge ratios (m/z). RESULTS: PTR-TOF-MS analysis was able to detect 167 features in exhaled breath from CF patients and healthy controls. According to cluster analysis and LASSO regression, patients with CF and controls were separated. The most significant VOCs for CF were indole, phenol, dimethyl sulfide, and not indicated: m/z = 297.0720 ([C12H13N2O7 and C17H13O5]H + ), m/z = 281.0534 ([C19H7NO2, C12H11NO7 and C16H9O5]H + ) during five-fold cross-validation both in forced expiratory maneuver and in normal quiet breathing. CONCLUSION: PTR-TOF-MS is a promising method for determining the molecular composition of exhaled air specific to CF.

Preparation of Protein Aerogel Particles for the Development of Innovative Drug Delivery Systems.

The research was oriented towards the preparation of aerogel particles based on egg white and whey protein isolate using various dispersion methods: dripping, spraying, and homogenization. Based on the results of analytical studies, the most appropriate samples were selected to obtain aerogels loaded with the drug. The results of the experimental research were used to study methods for obtaining nasal drug delivery systems based on aerogels. Protein aerogels were obtained by thermal gelation followed by supercritical drying. The obtained particles of protein aerogels have a specific surface area of up to 350 m2/g with a pore volume of up to 2.9 cm3/g, as well as a porosity of up to 95%. The results of experimental studies have shown that changing the dispersion method makes it possible to control the structural characteristics of protein aerogel particles. The results of the studies were applied to obtain innovative nasal drug delivery systems for the treatment of socially significant diseases. Analytical studies were conducted to determine the amount and state of adsorbed drugs in protein aerogel particles, as well as in vivo experiments on the distribution of clomipramine in blood plasma and brain tissue of rats to study the pharmacokinetics and bioavailability of the resulting drug-loaded protein aerogel.

Chitosan Aerogel Particles as Nasal Drug Delivery Systems.

The nasal drug delivery route has distinct advantages, such as high bioavailability, a rapid therapeutic effect, non-invasiveness, and ease of administration. This article presents the results of a study of the processes for obtaining chitosan aerogel particles that are promising as nasal or inhalation drug delivery systems. Obtaining chitosan aerogel particles includes the following steps: the preparation of a chitosan solution, gelation, solvent replacement, and supercritical drying. Particles of chitosan gels were obtained by spraying and homogenization. The produced chitosan aerogel particles had specific surface areas of up to 254 m2/g, pore volumes of up to 1.53 cm3/g, and porosities of up to 99%. The aerodynamic diameters of the obtained chitosan aerogel particles were calculated, the values of which ranged from 13 to 59 µm. According to the calculation results, a CS1 sample was used as a matrix for obtaining the pharmaceutical composition "chitosan aerogel-clomipramine". X-ray diffraction (XRD) analysis of the pharmaceutical composition determined the presence of clomipramine, predominantly in an amorphous form. Analysis of the high-performance liquid chromatography (HPLC) data showed that the mass loading of clomipramine was 35%. Experiments in vivo demonstrated the effectiveness of the pharmaceutical composition "chitosan aerogel-clomipramine" as carrier matrices for the targeted delivery of clomipramine by the "Nose-to-brain" mechanism of nasal administration. The maximum concentration of clomipramine in the frontal cortex and hippocampus was reached 30 min after administration.

Proteomic dataset: Profiling of glioma C6 and astrocytes rat cell lines before and after co-cultivation.

Human multiforme glioblastoma is characterized by an unfavorable prognosis, low survival rate and extremely limited possibilities for therapy. Rat C6 glioma is an experimental model for the study of glioblastoma growth and invasion. It has been shown that the growth and development of the tumor is accompanied by changes in the surrounding normotypic tissues [1]. These changes create a favorable environment for the development of the tumor and give it an evolutionary advantage [2]. Description of changes occurring in normotypic cells of the body upon their contact with tumor cells is of great interest. We have grown C6 glioma cells and rat astrocytes, as well as astrocyte cells co-cultured together with C6 glioma. We performed proteome-wide LC-MS analysis of these experimental groups. The data includes LC-MS/MS raw files and exported MaxQuant and ProteinPilot search results with fasta. Dataset published in the PRIDE repository project accession PXD026776.

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression.

BACKGROUND: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. METHODS: Rats' behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. RESULTS: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.

Current and Future Trends on Diagnosis and Prognosis of Glioblastoma: From Molecular Biology to Proteomics.

Glioblastoma multiforme is the most aggressive malignant tumor of the central nervous system. Due to the absence of effective pharmacological and surgical treatments, the identification of early diagnostic and prognostic biomarkers is of key importance to improve the survival rate of patients and to develop new personalized treatments. On these bases, the aim of this review article is to summarize the current knowledge regarding the application of molecular biology and proteomics techniques for the identification of novel biomarkers through the analysis of different biological samples obtained from glioblastoma patients, including DNA, microRNAs, proteins, small molecules, circulating tumor cells, extracellular vesicles, etc. Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.