Corneal alkali burns are potentially blinding injuries. Alkali induces oxidative stress in corneas followed by excessive corneal inflammation, neovascularization, and untransparent scar formation. Molecular hydrogen (H2), a potent reactive oxygen species (ROS) scavenger, suppresses oxidative stress and enables corneal healing when applied on the corneal surface. The purpose of this study was to examine whether the H2 pretreatment of healthy corneas evokes a protective effect against corneal alkali-induced oxidative stress. Rabbit eyes were pretreated with a H2 solution or buffer solution, by drops onto the ocular surface, and the corneas were then burned with 0.25 M NaOH. The results obtained with immunohistochemistry and pachymetry showed that in the corneas of H2-pretreated eyes, slight oxidative stress appeared followed by an increased expression of antioxidant enzymes. When these corneas were postburned with alkali, the alkali-induced oxidative stress was suppressed. This was in contrast to postburned buffer-pretreated corneas, where the oxidative stress was strong. These corneas healed with scar formation and neovascularization, whereas corneas of H2-pretreated eyes healed with restoration of transparency in the majority of cases. Corneal neovascularization was strongly suppressed. Our results suggest that the corneal alkali-induced oxidative stress was reduced via the increased antioxidant capacity of corneal cells against reactive oxygen species (ROS). It is further suggested that the ability of H2 to induce the increase in antioxidant cell capacity is important for eye protection against various diseases or external influences associated with ROS production.
- MeSH
- alkálie toxicita MeSH
- antioxidancia metabolismus MeSH
- chemické popálení farmakoterapie metabolismus patologie MeSH
- epitelové buňky účinky léků metabolismus patologie MeSH
- hojení ran účinky léků MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- neovaskularizace rohovky prevence a kontrola MeSH
- oxidační stres účinky léků MeSH
- popálení oka chemicky indukované farmakoterapie metabolismus patologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rohovka krevní zásobení účinky léků metabolismus patologie MeSH
- vodík farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Our previous research revealed that trehalose, a nonreducing disaccharide of glucose and an important stress responsive factor, proved to have anti-inflammatory, antiapoptotic, and particularly antioxidant properties in UVB-irradiated corneas. Trehalose reduced oxidative stress in corneas induced by UVB irradiation, by means of a decrease in the antioxidant/prooxidant imbalance in the corneal epithelium. In this study, we demonstrate that trehalose of 3% or 6% concentration in eye drops directly decreases oxidative stress in UVB-irradiated corneas, by removing the excessive amount of reactive oxygen species (ROS). Trehalose drops applied on corneas during UVB irradiation once daily for four days resulted in a reduction or even absence of the oxidative stress, DNA damage, and peroxynitrite formation (detected by nitrotyrosine residues), seen in buffer-treated corneas. Furthermore, trehalose treatment applied curatively after repeated irradiation for the subsequent fourteen days led to the renewal of corneal transparency and significant suppression or even absence of neovascularization. This was in contrast to buffer-treated irradiated corneas, where the intracorneal inflammation was developed and the untransparent corneas were vascularized. In conclusion, the treatment of UVB-irradiated corneas with trehalose eye drops removed the excessive amount of ROS in the corneal epithelium, leading to the suppression of oxidative stress and favorable corneal healing. The 6% trehalose showed a higher intensive antioxidant effect.
- MeSH
- hojení ran účinky léků účinky záření MeSH
- interleukin-1beta metabolismus MeSH
- keratiny metabolismus MeSH
- králíci MeSH
- oxidační stres * účinky léků účinky záření MeSH
- poranění rohovky farmakoterapie MeSH
- poškození DNA MeSH
- reaktivní formy kyslíku metabolismus MeSH
- reepitalizace účinky léků účinky záření MeSH
- rohovka účinky léků patologie účinky záření MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- trehalosa farmakologie terapeutické užití MeSH
- tyrosin analogy a deriváty metabolismus MeSH
- ultrafialové záření * MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Oxidative stress initiates, accompanies and contributes to the development of several human diseases and injuries, including ocular diseases. Reactive oxygen species (ROS) can generate oxidative stress via excessive ROS production and/or decreased physiologically occurring antioxidants. To replace these weakened antioxidants, substances with effective antioxidant properties are needed in order to suppress oxidative stress and enable healing. Molecular hydrogen (H2) is very suitable for this purpose due to its unique properties. H2 is the only antioxidant that crosses the blood-brain and blood-ocular barriers. It quickly penetrates through tissue due to its small molecular size and effectively removes ROS, mainly hydroxyl radicals and peroxynitrite. Apart from its antioxidant effects, H2 also displays anti-inflammatory, antiapoptotic, cytoprotective and mitohormetic properties. A significant advantage of H2 is its nontoxicity, even when applied at high concentrations. In this review, we present the results of studies utilising H2 in the treatment of ocular diseases involving oxidative stress. These results, obtained in experimental animals as well as in human clinical studies, show that the suppression of oxidative stress by H2 treatment leads to the prevention or improvement of ocular diseases. In severe degenerative diseases, H2 slows disease progression.
- MeSH
- lidé MeSH
- oční nemoci farmakoterapie patologie MeSH
- oxidační stres účinky léků MeSH
- vodík farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Many new therapeutic candidates and active pharmaceutical ingredients (APIs) are poorly soluble in an aqueous environment, resulting in their reduced bioavailability. A promising way of enhancing the release of an API and, thus, its bioavailability seems to be the use of liquid oil marbles (LOMs). An LOM system behaves as a solid form but consists of an oil droplet in which an already dissolved API is encapsulated by a powder. This study aims to optimize the oil/powder combination for the development of such systems. LOMs were successfully prepared for 15 oil/powder combinations, and the following properties were investigated: particle mass fraction, dissolution time, and mechanical stability. Furthermore, the release of API from both LOMs and LOMs encapsulated into gelatine capsules was studied.
- MeSH
- biologická dostupnost MeSH
- časové faktory MeSH
- farmaceutická chemie MeSH
- nosiče léků chemie MeSH
- oleje chemie MeSH
- prášky, zásypy, pudry MeSH
- příprava léků metody MeSH
- rozpustnost MeSH
- stabilita léku MeSH
- tobolky MeSH
- uvolňování léčiv MeSH
- voda chemie MeSH
- želatina chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The wide use of human multipotent mesenchymal stromal cells (MSCs) in clinical trials requires a full-scale safety and identity evaluation of the cellular product and subsequent transportation between research/medical centres. This necessitates the prolonged hypothermic storage of cells prior to application. The development of new, nontoxic, and efficient media, providing high viability and well-preserved therapeutic properties of MSCs during hypothermic storage, is highly relevant for a successful clinical outcome. In this study, a simple and effective trehalose-based solution was developed for the hypothermic storage of human bone marrow MSC suspensions for further clinical applications. Human bone marrow MSCs were stored at 4°C for 24, 48, and 72 hrs in the developed buffered trehalose solution and compared to several research and clinical grade media: Plasma-Lyte® 148, HypoThermosol® FRS, and Ringer's solution. After the storage, the preservation of viability, identity, and therapeutically associated properties of MSCs were assessed. The hypothermic storage of MSCs in the new buffered trehalose solution provided significantly higher MSC recovery rates and ability of cells for attachment and further proliferation, compared to Plasma-Lyte® 148 and Ringer's solution, and was comparable to research-grade HypoThermosol® FRS. There were no differences in the immunophenotype, osteogenic, and adipogenic differentiation and the immunomodulatory properties of MSCs after 72 hrs of cold storage in these solutions. The obtained results together with the confirmed therapeutic properties of trehalose previously described provide sufficient evidence that the developed trehalose medium can be applied as a low-cost and efficient solution for the hypothermic storage of MSC suspensions, with a high potential for translation into clinical practice.
- Publikační typ
- časopisecké články MeSH
Trehalose, a disaccharide of glucose, is a naturally occurring nontoxic and nonreducing bioactive sugar. Trehalose is synthetized by many organisms when cells are exposed to stressful conditions, including dehydration, heat, oxidation, hypoxia or even anoxia. Although trehalose is not synthesized by mammalian cells, it has recently been demonstrated to have a number of important properties that indicate its utility in humans. Trehalose enables wound healing by protecting cells, especially cell membranes, from oxidative injury and dessication. When the injured cornea is treated with trehalose, corneal inflammation, scar formation and corneal neovascularization are suppressed. In dry eye disease, trehalose decreased cell apoptosis and reduced oxidative, inflammatory and proteolytic activity at the ocular surface. In UVB irradiated cornea, trehalose suppressed photodamage evoked by UVB rays. It decreased the intracorneal inflammation and reduced corneal neovascularization. Trehalose prevented postoperative fibrous scar formation after ocular surgery, such as glaucoma filtration surgery. The non-toxicity of trehalose allows its administration in humans for extended periods and enables its use in various disease states.
- MeSH
- antiflogistika chemie farmakologie MeSH
- antioxidancia chemie farmakologie MeSH
- apoptóza * MeSH
- hojení ran * MeSH
- klinické zkoušky jako téma MeSH
- králíci MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- oftalmologie MeSH
- oxidační stres * MeSH
- rohovka účinky léků účinky záření MeSH
- syndromy suchého oka farmakoterapie MeSH
- trehalosa chemie farmakologie MeSH
- ultrafialové záření MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Protocells are objects that mimic one or several functions of biological cells and may be embodied as solid particles, lipid vesicles, or droplets. Our work is based on using decanol droplets in an aqueous solution of sodium decanoate in the presence of salt. A decanol droplet under such conditions bears many qualitative similarities with living cells, such as the ability to move chemotactically, divide and fuse, or change its shape. This article focuses on the description of a shape-changing process induced by the evaporation of water from the decanoate solution. Under these conditions, the droplets perform complex shape changes, whereby the originally round decanol droplets grow into branching patterns and mimic the growth of appendages in bacteria or axon growth of neuronal cells. We report two outcomes: (i) the morphological changes are reversible, and (ii) multiple protocells avoid contact between each other during the morphological transformation. The importance of these morphological changes in the context of artificial life are discussed.
The aim of this study is to examine whether molecular hydrogen (H2) is able to reduce oxidative stress after corneal damage induced by UVB irradiation. We previously found that UVB irradiation of the cornea caused the imbalance between the antioxidant and prooxidant enzymes in the corneal epithelium, followed by the imbalance between metalloproteinases and their physiological inhibitors (imbalances in favour of prooxidants and metalloproteinases) contributing to oxidative stress and development of the intracorneal inflammation. Here we investigate the effect of H2 dissolved in PBS in the concentration 0.5 ppm wt/vol, applied on rabbit corneas during UVB irradiation and healing (UVB doses 1.01 J/cm2 once daily for four days). Some irradiated corneas remained untreated or buffer treated. In these corneas the oxidative stress appeared, followed by the excessive inflammation. Malondiladehyde and peroxynitrite expressions were present. The corneas healed with scar formation and neovascularization. In contrast, in H2 treated irradiated corneas oxidative stress was suppressed and malondiladehyde and peroxynitrite expressions were absent. The corneas healed with the restoration of transparency. The study provides the first evidence of the role of H2 in prevention of oxidative and nitrosative stress in UVB irradiated corneas, which may represent a novel prophylactic approach to corneal photodamage.
- MeSH
- králíci MeSH
- kyselina peroxydusitá metabolismus MeSH
- malondialdehyd metabolismus MeSH
- oxidační stres účinky léků účinky záření MeSH
- poranění rohovky farmakoterapie metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rohovka účinky léků metabolismus účinky záření MeSH
- ultrafialové záření * MeSH
- vodík terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- odvolaná publikace MeSH
- práce podpořená grantem MeSH
Liquid droplets are very simple objects present in our everyday life. They are extremely important for many natural phenomena as well as for a broad variety of industrial processes. The conventional research areas in which the droplets are studied include physical chemistry, fluid mechanics, chemical engineering, materials science, and micro- and nanotechnology. Typical studies include phenomena such as condensation and droplet formation, evaporation of droplets, or wetting of surfaces. The present article reviews the recent literature that employs droplets as animated soft matter. It is argued that droplets can be considered as liquid robots possessing some characteristics of living systems, and such properties can be applied to unconventional computing through maze solving or operation in logic gates. In particular, the lifelike properties and behavior of liquid robots, namely (i) movement, (ii) self-division, and (iii) group dynamics, will be discussed.
