ABSTRACT
BACKGROUND: Cerebral aneurysms (CA) are a widespread vascular disease affecting 50 per 1000 population. The study of the influence of histological, morphological and hemodynamic factors on the status of the aneurysm has been the subject of many works. However, an accurate and generally accepted relationship has not yet been identified. METHODS: In our work, the results of mechanical and spectroscopic measurements are considered. Total investigated 14 patients and 36 their samples of CA tissue. RESULTS: The excitation-emission matrix of each specimen was evaluated, after which the strength characteristics of the samples were investigated. CONCLUSIONS: It has been shown that there is a statistically significant difference in the size of the peaks of two components, which characterizes the status of the aneurysms. In addition, a linear regression model has been built that describes the correlation of the magnitude of the ultimate strain and stress with the magnitude of the peaks of one of the components. The results of this study will serve as a basis for the non-invasive determination of the strength characteristics of the cerebral tissue aneurysms and determination of their status.
ABSTRACT
The human parasite Plasmodium falciparum kills an estimated 445,000 people a year, with the most fatalities occurring in African children. Previous studies identified falcilysin (FLN) as a malarial metalloprotease essential for parasite development in the human host. Despite its essentiality, the biological roles of this protease are not well understood. Here we describe the optimization of a piperazine-based hydroxamic acid scaffold to develop the first reported inhibitors of FLN. Inhibitors were tested against cultured parasites, and parasiticidal activity correlated with potency against FLN. This suggests these compounds kill P. falciparum by blocking FLN, and that FLN is a druggable target. These compounds represent an important step towards validating FLN as a therapeutic target and towards the development of chemical tools to investigate the function of this protease.
Subject(s)
Antimalarials/chemistry , Hydroxamic Acids/chemistry , Metalloendopeptidases/antagonists & inhibitors , Piperazine/chemistry , Protease Inhibitors/chemistry , Protozoan Proteins/antagonists & inhibitors , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Hydroxamic Acids/chemical synthesis , Hydroxamic Acids/pharmacology , Inhibitory Concentration 50 , Metalloendopeptidases/metabolism , Plasmodium falciparum/drug effects , Plasmodium falciparum/enzymology , Protease Inhibitors/chemical synthesis , Protease Inhibitors/pharmacology , Protozoan Proteins/metabolism , Structure-Activity RelationshipABSTRACT
Many conventional biochemical assays are performed using populations of cells to determine their quantitative biomolecular profiles. However, population averages do not reflect actual physiological processes in individual cells, which occur either on short time scales or nonsynchronously. Therefore, accurate analysis at the single-cell level has become a highly attractive tool for investigating cellular content. Microfluidic chips with arrays of microwells were developed for single-cell chemical lysis in the present study. The cellular occupancy in 30-µm-diameter microwells (91.45%) was higher than that in 20-µm-diameter microwells (83.19%) at an injection flow rate of 2.8 µL/min. However, most of the occupied 20-µm-diameter microwells contained individual cells. The results of chemical lysis experiments at the single-cell level indicate that cell membranes were gradually lysed as the lysis buffer was injected; they were fully lysed after 12 s. Single-cell chemical lysis was demonstrated in the proposed microfluidic chip, which is suitable for high-throughput cell lysis.
