Advancements of plasma science, such as the development of cold atmospheric plasmas made it possible to easily generate reactive oxygen and nitrogen species (RONS) and apply them to biological media under ambient conditions. Studying the interactions of RONS with biomolecules is a central topic of plasma medicine. One of the main targets of plasma medicine is to take control over signaling proteins such as human epidermal growth factor (hEGF) which is an important protein in cancer treatment and wound healing. The oxidative damage of RONS on various proteins, including hEGF, was investigated using molecular dynamics (MD) simulations. However, another effect of RONS – nitrosative damage – is left unexplored. Plasma treatment can induce substantial damage via nitrosylation by reactive nitrogen species. Thus, elucidating the effects of nitrosylation on protein structures is crucial, especially in plasma medicine. Here, we perform MD simulations to explore the effect of nitrosylation on the conformation of hEGF. We carried out MD simulations with different degrees of modifications of hEGF structures to mimic short and long plasma exposure times. Our results show that nitrosylation induces conformational changes in hEGF and the breakage of disulfide bonds which might modulate the binding of hEGF with its receptor. But the structural stability of hEGF remains almost unchallenged to the nitrosative damage, even to the disruption of disulfide bonds. The results assist plasma medicine applications in cancer treatment and wound healing by modulating plasma treatment time and chemical compositions of plasma-generated RONS to mediate effective oxidation of the biological environment and develop optimal treatment protocols.

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Due to their potential benefits, cold atmospheric plasmas (CAPs), as biotechnological tools, have been used for various purposes, especially in medical and agricultural applications. The main effect of CAP is associated with reactive oxygen and nitrogen species (RONS). In order to deliver these RONS to the target, direct or indirect treatment approaches have been employed. The indirect method is put into practice via plasma-activated water (PAW). Despite many studies being available in the field, the permeation mechanisms of RONS into water at the molecular level still remain elusive. Here, we performed molecular dynamics simulations to study the permeation of RONS from vacuum into the water interface and bulk. The calculated free energy profiles unravel the most favourable accumulation positions of RONS. Our results, therefore, provide fundamental insights into PAW and RONS chemistry to increase the efficiency of PAW in biological applications.

Horse chestnut (Aesculus hippocastanum L.)-derived drugs have shown their potential in biomedical applications. The seed of A. hippocastanum contains various kinds of chemical compounds including phenolics, flavonoids, coumarins, and triterpene saponins. Here, we investigated the chemical components in A. hippocastanum L. grown in Uzbekistan, which has not yet been studied in detail. We identified 30 kinds of triterpene saponins in an extract of A. hippocastanum L. Classifying extracted saponins into eight fractions, we next studied the hypoglycemic and the anti-inflammatory activities of escin and its derivatives through in vivo experiments. We came by data indicating the highest (SF-1 and SF-2) and the lowest (SF-5 and SF-8) antidiabetic and anti-inflammatory effects of those eight fractions. These results imply the prospective use of A. hippocastanum L. grown in Uzbekistan in the production of pharmaceutical drugs to treat diabetes and inflammation.

The three-dimensional structure of a peptide, which determines its function, can denature at elevated temperatures, in the presence of chaotropic reagents, or in organic solvents. These factors limit the applicability of peptides. Herein, we present an engineered β-hairpin peptide containing a His 3 site that forms complexes with Zn II , Ni II , and Cu II . Circular dichroism spectroscopy shows that the peptideÀ metal complexes exhibit melting temperatures up to 80 °C and remain folded in 6 M guanidine hydrochloride as well as in organic solvents. Intrinsic fluorescence titration experiments were used to determine the dissociation constants of metal binding in the nano-to subnanomolar range. The coordination geometry of the peptideÀ Cu II complex was studied by EPR spectroscopy, and a distorted square planar coordination geometry with weak interactions to axial ligands was revealed. Due to their impressive stability, the presented peptideÀ metal complexes open up interesting fields of application, such as the development of a new class of peptideÀ metal catalysts for stereoselective organic synthesis or the directed design of extremophilic β-sheet peptides.

The self-association of amylogenic proteins to the fibril form is considered a pivotal factor in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). PD causes unintended or uncontrollable movements in its common symptoms. α-synuclein is the major cause of PD development and thus has been the main target of numerous studies to suppress and sequester its expression or effectively degrade it. Nonetheless, to date, there are no efficient and proven ways to prevent pathological protein aggregation. Recent investigations proposed applying an external electric field to interrupt the fibrils. This method is a non-invasive approach that has a certain benefit over others. We performed molecular dynamics (MD) simulations by applying an electric field on highly toxic fibrils of α-synuclein to gain a molecular-level insight into fibril disruption mechanisms. The results revealed that the applied external electric field induces substantial changes in the conformation of the α-synuclein fibrils. Furthermore, we show the threshold value for electric field strength required to completely disrupt the α-synuclein fibrils by opening the hydrophobic core of the fibril. Thus, our findings might serve as a valuable foundation to better understand molecular-level mechanisms of the α-synuclein fibrils disaggregation process under an applied external electric field.

Although modern medicine is advancing at an unprecedented rate, basic challenges in cancer treatment and drug resistance remain. Exploiting natural-product-based drugs is a strategy that has been proven over time to provide diverse and efficient approaches in patient care during treatment and post-treatment periods of various diseases, including cancer. Escin—a plant-derived triterpenoid saponin—is one example of natural products with a broad therapeutic scope. Initially, escin was proven to manifest potent anti-inflammatory and anti-oedematous effects. However, in the last two decades, other novel activities of escin relevant to cancer treatment have been reported. Recent studies demonstrated escin’s efficacy in compositions with other approved drugs to accomplish synergy and increased bioavailability to broaden their apoptotic, anti-metastasis, and anti-angiogenetic effects. Here, we comprehensively discuss and present an overview of escin’s chemistry and bioavailability, and highlight its biological activities against various cancer types. We conclude the review by presenting possible future directions of research involving escin for medical and pharmaceutical applications as well as for basic research.

Iodine, being an intrinsic part of thyroid hormones, is a vital microelement required for normal growth and development, particularly in children. Inadequate daily intake of iodine causes iodine deficiency, which is responsible for several health disorders, such as cretinism and goiters. Therefore, the development of new drugs and/or food supplements for iodine deficiency is crucial. We synthesized an iodine/β-cyclodextrin complex based on a host–guest model, and in this paper, we outline the development of a new quantitative analysis method. We suggest a robust and reliable high-performance liquid chromatography method to determine the total amount of iodine species in the complex. Moreover, we performed validation of our method. The results of validation presented here show the reliability, accuracy and high precision of the method. Furthermore, for the first time, we show results of in vivo studies for the thyroid-stimulating activity of the iodine/β-cyclodextrin complex. Our findings indicate that the thyroid-stimulating activity of iodine/β-cyclodextrin is comparable to that of potassium iodide, which is the main active pharmaceutical substance of conventional drugs for iodine deficiency.