Tapinarof (3,5-dihydroxy-4-isopropylstilbene) is a therapeutic agent used in the treatment of psoriasis (VTAMA®). In this study, we examined the redox behaviour, (photo)stability, (photo)toxicity and (bio)transformation of tapinarof in the context of a structure-activity relationship study. Selected derivatives of the structurally related tapinarof were investigated, namely resveratrol, pterostilbene, pinosylvin and its methyl ether. Tapinarof undergoes electrochemical oxidation in a neutral aqueous medium at a potential of around +0.5 V (vs. Ag|AgCl|3M KCl). The anodic reaction of this substance is a proton-dependent irreversible and adsorption-driven process. The pKa value of tapinarof corresponds to 9.19 or 9.93, based on empirical and QM calculation approach, respectively. The oxidation potentials of tapinarof and its analogues correlate well with their HOMO (highest occupied molecular orbital) energy level. The ability to scavenge the DPPH radical decreased in the order trolox ≥ resveratrol > pterostilbene > tapinarof > pinosylvin ≫ pinosylvin methyl ether. It was also confirmed that tapinarof, being a moderate electron donor, is able to scavenge the ABTS radical and inhibit lipid peroxidation. The 4'-OH group plays a pivotal role in antioxidant action of stilbenols. During the stability studies, it was shown that tapinarof is subject to spontaneous degradation under aqueous conditions, and its degradation is accelerated at elevated temperatures and after exposure to UVA (315-399 nm) radiation. In aqueous media at pH 7.4, we observed an ∼50 % degradation of tapinarof after 48 h at laboratory temperature. The main UVA photodegradation processes include dihydroxylation and hydration. In conclusion, the phototoxic effect of tapinarof on a human keratinocytes cell line (HaCaT) was evaluated. Tapinarof exhibited a clear phototoxic effect, similar to phototoxic standard chlorpromazine. The IC50 values of the cytotoxicity and phototoxic effects of tapinarof correspond to 27.6 and 3.7 μM, respectively. The main HaCaT biotransformation products of tapinarof are sulfates and glucuronides.
- MeSH
- Antioxidants pharmacology chemistry MeSH
- HaCaT Cells MeSH
- Dermatitis, Phototoxic MeSH
- Keratinocytes * drug effects metabolism radiation effects MeSH
- Skin drug effects metabolism radiation effects pathology MeSH
- Humans MeSH
- Oxidation-Reduction * MeSH
- Resveratrol pharmacology analogs & derivatives chemistry MeSH
- Stilbenes * pharmacology chemistry MeSH
- Ultraviolet Rays MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The study aimed to investigate changes in the eye axial length in juvenile guinea pigs and the expression of scleral specificity protein 1 (Sp1) and collagen type I (Col-I) under different light environments with varying spectral composition. The animals were randomly divided into five groups: natural light (N), LED light with a low colour temperature (L), E light (E), Fulia light (F), and Gulia light (G). Axial lengths were measured every two weeks, and the expression of Sp1 and Col-I in the sclera was assessed by immunohistochemistry, Western blot and RT-qPCR. After 4, 6, 8, 10, and 12 weeks of light exposure, the L and G groups showed considerably longer axial lengths than the N group, with the L group exhibiting significantly longer axial lengths compared with the E and F groups. The protein and mRNA expression levels of Sp1 and Col-I, ranked from highest to lowest, were as follows: N, E, F, G, and L. The expression of Sp1 and Col-I was positively correlated, but both were negatively correlated with the length of the eye axis. The E group demonstrated higher Sp1 and Col-I expression than the other artificial light groups. Artificial light with a continuous, full spectrum lacking peaks and valleys can inhibit the elongation of the eye axis in juvenile guinea pigs and has a protective effect against myopia. There may be a certain relationship between Sp1 and Col-I, and the transforming growth factor-β1-Sp1-Col-I signalling pathway may play a crucial role in myopic scleral extracellular matrix remodelling.
- MeSH
- Axial Length, Eye MeSH
- Collagen Type I * metabolism genetics MeSH
- RNA, Messenger metabolism genetics MeSH
- Guinea Pigs MeSH
- Myopia metabolism genetics pathology MeSH
- Gene Expression Regulation MeSH
- Sclera * metabolism MeSH
- Light * MeSH
- Sp1 Transcription Factor * metabolism genetics MeSH
- Animals MeSH
- Check Tag
- Guinea Pigs MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Dunaliella salina is a rich source of carotenoids. Carotenoid production is induced under specific conditions, i.e., high light intensity, high salt concentration, nutrient limitation, and suboptimal temperatures in this microalga. The control of environmental factors is vital for high productivity of carotenoids. In this paper, the effect of different ethanol concentrations in combination with nitrogen deficiency was investigated to induce carotenoid production in D. salina CCAP 19/18. Also, some biochemical and molecular parameters were investigated in response to ethanol in the cells. It was shown that ethanol at 0.5% concentration increased cell number but, at 5% concentration, reduced cell viability compared to the control. The highest carotenoid production was achieved at 3% ethanol concentration, which was 1.46 fold higher than the nitrogen deficiency condition. Investigation of the 3 carotenoid biosynthesis genes revealed that their expression levels increased at 3% ethanol concentration, and the phytoene synthase gene was the most upregulated one. Lipid peroxidation increased at both 3% and 5% ethanol concentrations. At 3% concentration, the activity of catalase and superoxide dismutase increased, but no significant changes were seen at 5% ethanol concentration. Peroxidase activity reduced at both 3% and 5% concentrations. Moreover, proline and reducing sugar content increased at 3% concentration while decreased at 5% ethanol concertation. The results showed that at 3% ethanol concentration, higher carotenoid productivity was associated with an increase in other intracellular responses (molecular and biochemical). Ethanol as a controllable element may be beneficial to increase carotenoid production even under inappropriate environmental conditions in D. salina.
- MeSH
- Antioxidants * MeSH
- Nitrogen MeSH
- Carotenoids * metabolism MeSH
- Superoxide Dismutase metabolism MeSH
- Light MeSH
- Publication type
- Journal Article MeSH
This paper introduces a new class of amphiphilic block copolymers created by combining two polymers: polylactic acid (PLA), a biocompatible and biodegradable hydrophobic polyester used for cargo encapsulation, and a hydrophilic polymer composed of oligo ethylene glycol chains (triethylene glycol methyl ether methacrylate, TEGMA), which provides stability and repellent properties with added thermo-responsiveness. The PLA-b-PTEGMA block copolymers were synthesized using ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization (ROP-RAFT), resulting in varying ratios between the hydrophobic and hydrophilic blocks. Standard techniques, such as size exclusion chromatography (SEC) and 1H NMR spectroscopy, were used to characterize the block copolymers, while 1H NMR spectroscopy, 2D nuclear Overhauser effect spectroscopy (NOESY), and dynamic light scattering (DLS) were used to analyze the effect of the hydrophobic PLA block on the LCST of the PTEGMA block in aqueous solutions. The results show that the LCST values for the block copolymers decreased with increasing PLA content in the copolymer. The selected block copolymer presented LCST transitions at physiologically relevant temperatures, making it suitable for manufacturing nanoparticles (NPs) and drug encapsulation-release of the chemotherapeutic paclitaxel (PTX) via temperature-triggered drug release mechanism. The drug release profile was found to be temperature-dependent, with PTX release being sustained at all tested conditions, but substantially accelerated at 37 and 40 °C compared to 25 °C. The NPs were stable under simulated physiological conditions. These findings demonstrate that the addition of hydrophobic monomers, such as PLA, can tune the LCST temperatures of thermo-responsive polymers, and that PLA-b-PTEGMA copolymers have great potential for use in drug and gene delivery systems via temperature-triggered drug release mechanisms in biomedicine applications.
- Publication type
- Journal Article MeSH
The strong antifungal effect of sulfonated polystyrene nanoparticles (NPs) with an encapsulated tetraphenylporphyrin (TPP) photosensitizer is reported here. TPP is activated by visible light, resulting in the generation of singlet oxygen. Its antifungal action is potentiated in the presence of potassium iodide, yielding I2/I3−, another antifungal species. The NPs exhibit no dark toxicity, but a broad spectrum of antifungal photodynamic effects. The efficiency of this rapid killing (on the order of minutes) depends on the concentration of TPP NPs, potassium iodide, yeast species and temperature. A strong antifungal activity of TPP NPs is demonstrated on eleven pathogenic and opportunistic pathogenic yeast species (six Candida species and other yeast species, including melanized Hortaea werneckii). The composition and architecture of yeast cell envelope structures clearly influence the efficacy of photodynamic therapy. Candida krusei is the most sensitive to photodynamic therapy. Despite expectations, melanin does not provide Hortaea cells with marked resistance compared to white yeast species. The kinetics of the interaction of NPs with yeast cells is also described. This study may inspire and promote the fabrication of a new type of antiseptic for various skin injuries in clinical medicine.
- MeSH
- Antifungal Agents pharmacology therapeutic use MeSH
- Photochemotherapy * MeSH
- Photosensitizing Agents pharmacology chemistry therapeutic use MeSH
- Potassium Iodide chemistry pharmacology MeSH
- Nanoparticles * chemistry MeSH
- Porphyrins * pharmacology chemistry MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Electronic nicotine delivery systems (ENDS) generate an aerosol by vaporising e-liquids that usually consist of propylene glycol (PG), vegetable glycerine (VG), and other ingredients (water, nicotine, and flavours). The chemical and physical properties of these components have a significant effect on aerosol formation and must be identified in order to improve product attractiveness and assess the degree of health risks. AIM: The aim of this article is to provide a description of the composition of the e-liquid base and its impact on the physical properties of the liquid used and the behaviour of the aerosol generated and particles separately. METHODS: For this purpose, 46 articles were selected using a series of keywords. English- language publications were chosen. RESULTS: The impact of the PG/VG ratio on the physical properties of the e-liquid (boiling point, viscosity, volatility, hygroscopicity), aerosol emission characteristics (refractive index, light scattering coefficient, particle size distribution, concentration, emission of harmful compounds), vape attractiveness (taste, “throat-hit”, “cloud effect”), nicotine flux, coil temperature, and puff topography is presented. CONCLUSIONS: The PG/VG ratio is strongly correlated with the emission of carbonyls, which has adverse health effects and should be optimised. Furthermore, PG and VG also affect the other important characteristics of the aerosol generated by ENDS, which impact on both attractiveness and the consumption of harmful compounds. These findings could be considered for further research with the aim of improving electronic nicotine delivery systems as this can reduce levels of toxicants. This can be achieved by optimising the geometry of the components with respect to heating power and e-liquid.
Tento přehled si klade za cíl seznámit klinické a laboratorní pracovníky s nejdůležitějšími preanalytickými a analytickými aspekty stanovení lehkých řetězců neurofilament (NfL) v biologických tekutinách. NfL představují perspektivní nespecifický biomarker poškození neuronů a axonů, k němuž dochází u celé řady neurologických onemocnění. Před zavedením vyšetřování NfL do širší klinické praxe je nutné charakterizovat preanalytické a analytické stránky stanovení, které mohou významným způsobem ovlivnit správnost výsledku analýzy. Při hodnocení koncentrací NfL je zapotřebí brát v úvahu věk pacienta a vliv může mít i body mass index. Výhodou NfL je jejich dlouhodobá stabilita při různých teplotách skladování i odolnost vůči opakovaným cyklům zmrazování a rozmrazování. Koncentrace NfL v klinických studiích se stanovují především imunoanalytickými metodami, které se liší citlivostí. Pro stanovení NfL existuje několik imunoanalytických přístupů vhodných pro spolehlivé vyšetření v mozkomíšním moku (MMM) i v séru/plazmě. Volba optimálního analytického přístupu závisí mimo jiné na koncentracích NfL v biologických tekutinách. Pro stanovení NfL v MMM lze využít metod ELISA, které vykazují dostačující citlivost pro vyšší koncentrace NfL vyskytující se v této biologické tekutině. Postupně zaváděné nové technologie charakterizované výrazně vyšší citlivostí ve srovnání s metodou ELISA umožnily spolehlivé vyšetřování NfL i v séru či plazmě. Podrobněji jsou zmiňovány principy metod postavené na technologii Simoa®, SimplePlexTM a imunomagnetické redukce.
The aim of this review is to inform clinical and laboratory workers about the most important pre-analytical and analytical aspects of neurofilament light chain (NfL) determination in biological fluids. NfLs represent a promising nonspecific biomarker of neuronal and axonal damage that occurs in a variety of neurological diseases. Before introducing NfL determination into routine clinical practice, it is necessary to characterize the pre-analytical and analytical aspects of the assays, which can significantly affect the accuracy of the analysis results. When evaluating NfL concentrations, the patient‘s age should be taken into account and body mass index may also have an effect. The advantages of NfLs are their long-term storage stability at different temperatures as well as resistance to repeated freezing and thawing cycles. NfL concentrations in clinical trials are determined primarily by immunoassay methods that vary in sensitivity. There are several immunoassay technologies for the determination of NfL suitable for reliable determination in cerebrospinal fluid (CSF) and serum/plasma. The choice of the optimal analytical approach depends, among other things, on the concentration of NfL in biological fluids. ELISA methods can be used to determine NfL in CSF, which show sufficient sensitivity for higher concentrations of NfL occurring in this biological fluid. Newly introduced technologies characterized by significantly higher sensitivity in comparison with the ELISA methods enabled reliable examination of NfL also in serum/plasma. The principles of methods based on Simoa® technology, SimplePlexTM, and immunomagnetic reduction are mentioned in more detail.
- MeSH
- Biomarkers analysis chemistry MeSH
- Intermediate Filaments * chemistry MeSH
- Humans MeSH
- Cerebrospinal Fluid chemistry MeSH
- Pre-Analytical Phase methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Improving indoor lighting conditions at the workplace has the potential to support proper circadian entrainment of hormonal rhythms, sleep, and well-being. We tested the effects of optimized dynamic daylight and electric lighting on circadian phase of melatonin, cortisol and skin temperatures in office workers. We equipped one office room with an automated controller for blinds and electric lighting, optimized for dynamic lighting (= Test room), and a second room without any automated control (= Reference room). Young healthy participants (n = 34) spent five consecutive workdays in each room, where individual light exposure data, skin temperatures and saliva samples for melatonin and cortisol assessments were collected. Vertical illuminance in the Test room was 1177 ± 562 photopic lux (mean ± SD) , which was 320 lux higher than in the Reference room (p < 0.01). Melanopic equivalent daylight (D65) illuminance was 931 ± 484 melanopic lux in the Test room and 730 ± 390 melanopic lux in the Reference room (p < 0.01). Individual light exposures resulted in a 50 min earlier time of half-maximum accumulated illuminance in the Test than the Reference room (p < 0.05). The melatonin secretion onset and peripheral heat loss in the evening occurred significantly earlier with respect to habitual sleeptime in the Test compared to the Reference room (p < 0.05). Our findings suggest that optimized dynamic workplace lighting has the potential to promote earlier melatonin onset and peripheral heat loss prior bedtime, which may be beneficial for persons with a delayed circadian timing system.
- MeSH
- Circadian Rhythm MeSH
- Hydrocortisone MeSH
- Humans MeSH
- Melatonin * MeSH
- Lighting * MeSH
- Sleep MeSH
- Light MeSH
- Body Temperature Regulation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Lacking fur, living in eusocial colonies and having the longest lifespan of any rodent, makes naked mole-rats (NMRs) rather peculiar mammals. Although they exhibit a high degree of polymorphism, skeletal plasticity and are considered a novel model to assess the effects of delayed puberty on the skeletal system, scarce information on their morphogenesis exists. Here, we examined a large ontogenetic sample (n = 76) of subordinate individuals to assess the pattern of bone growth and bone microstructure of fore- and hindlimb bones by using histomorphological techniques. Over 290 undecalcified thin cross-sections from the midshaft of the humerus, ulna, femur, and tibia from pups, juveniles and adults were analyzed with polarized light microscopy. Similar to other fossorial mammals, NMRs exhibited a systematic cortical thickening of their long bones, which clearly indicates a conserved functional adaptation to withstand the mechanical strains imposed during digging, regardless of their chisel-tooth predominance. We describe a high histodiversity of bone matrices and the formation of secondary osteons in NMRs. The bones of pups are extremely thin-walled and grow by periosteal bone formation coupled with considerable expansion of the medullary cavity, a process probably tightly regulated and adapted to optimize the amount of minerals destined for skeletal development, to thus allow the female breeder to produce a higher number of pups, as well as several litters. Subsequent cortical thickening in juveniles involves high amounts of endosteal bone apposition, which contrasts with the bone modeling of other mammals where a periosteal predominance exists. Adults have bone matrices predominantly consisting of parallel-fibered bone and lamellar bone, which indicate intermediate to slow rates of osteogenesis, as well as the development of poorly vascularized lamellar-zonal tissues separated by lines of arrested growth (LAGs) and annuli. These features reflect the low metabolism, low body temperature and slow growth rates reported for this species, as well as indicate a cyclical pattern of osteogenesis. The presence of LAGs in captive individuals was striking and indicates that postnatal osteogenesis and its consequent cortical stratification most likely represents a plesiomorphic thermometabolic strategy among endotherms which has been suggested to be regulated by endogenous rhythms. However, the generalized presence of LAGs in this and other subterranean taxa in the wild, as well as recent investigations on variability of environmental conditions in burrow systems, supports the hypothesis that underground environments experience seasonal fluctuations that may influence the postnatal osteogenesis of animals by limiting the extension of burrow systems during the unfavorable dry seasons and therefore the finding of food resources. Additionally, the intraspecific variation found in the formation of bone tissue matrices and vascularization suggested a high degree of developmental plasticity in NMRs, which may help explaining the polymorphism reported for this species. The results obtained here represent a valuable contribution to understanding the relationship of several aspects involved in the morphogenesis of the skeletal system of a mammal with extraordinary adaptations.
- MeSH
- Femur anatomy & histology MeSH
- Humerus anatomy & histology MeSH
- Mole Rats MeSH
- Osteogenesis physiology MeSH
- Tibia anatomy & histology MeSH
- Ulna anatomy & histology MeSH
- Bone Development physiology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: The sun is a natural source of UV radiation. It can be divided into three bands, UVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm), where the radiation up to 290 nm is very effectively eliminated by the stratospheric ozone. Although UV radiation can have a beneficial effect on our organism and can be used in the treatment of several skin diseases, it must primarily be considered harmful. METHODS: In the presented work, we focused on the study of the longer-wavelength UV components (UVA and UVB) on the human epidermal keratinocyte line HaCaT. As UVA and UVB radiation sources, we used commercially available UVA and UVB tubes from Philips (Philips, Amsterdam, The Netherlands), which are commonly employed in photochemotherapy. We compared their effects on cell viability and proliferation, changes in ROS production, mitochondrial function and the degree of DNA damage. RESULTS: Our results revealed that UVB irradiation, even with significantly lower irradiance, caused greater ROS production, depolarization of mitochondrial membrane potential and greater DNA fragmentation, along with significantly lowering cell viability and proliferative capacity. CONCLUSIONS: These results confirm that UV radiation causes severe damages in skin cells, and they need to be protected from it, or it needs to be applied more cautiously, especially if the component used is UVB.
- MeSH
- HaCaT Cells MeSH
- Keratinocytes * radiation effects MeSH
- Skin MeSH
- Humans MeSH
- DNA Damage MeSH
- Ultraviolet Rays * adverse effects classification MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
