Search Results (27)

Objective: This study evaluated the systemic bioavailability of L-thyroxine (L-T4) in healthy women following repeated cutaneous application of a new gel formulation containing L-T4 and escin. Plasma concentrations of free triiodothyronine (FT3), reverse triiodothyronine (rT3), and thyroid-stimulating hormone (TSH) were also assessed, along with local and systemic tolerability. Methods: Thirty healthy women participated in a single-group, open-label trial. L-thyroxine gel was applied at 20 g/day for the first 2 days and 10 g/day for the following 26 days (equivalent to 20 mg/day and 10 mg/day of L-T4, respectively). Blood samples were collected at Baseline, 5 and 24 h after the first application, and on Days 14, 28 (End of Treatment, EOT), and 42 (End of Study, EOS). Tolerability and safety were monitored throughout. Results: Plasma FT4 concentrations remained stable throughout the study, with no clinically significant changes from Baseline (1.13 ± 0.15 ng/dL) to EOT (1.11 ± 0.13 ng/dL). FT3 and TSH levels also remained within physiological ranges, with only a transient, non-clinically relevant decrease observed 5 h after the first application. No changes in rT3 concentrations were detected at any time point. No serious adverse events were reported. Conclusions: This study confirms that repeated application of L-thyroxine/escin gel over 28 days (total exposure of 300 g) does not affect systemic thyroid hormone levels and is well tolerated in healthy women. These findings support the hypothesis that intact skin acts as an effective barrier to transdermal L-T4 absorption. Full article

The incorporation of selenium into tacrine derivatives has been explored as a novel strategy to enhance therapeutic efficacy while minimizing toxicity in the treatment of neurodegenerative diseases such as Alzheimer’s. This study utilized computational and experimental approaches, including Density Functional Theory (DFT), molecular docking, pharmacokinetic profiling, and toxicological predictions, to evaluate the potential of these derivatives. The selenium-modified compounds demonstrated improved electronic properties, such as narrower HOMO–LUMO gaps and optimized electronegativity, resulting in enhanced stability and reactivity. Pharmacokinetic analyses revealed favorable absorption, distribution, and blood–brain barrier penetration, while toxicological assessments indicated reduced hepatotoxicity and skin sensitization risks compared to tacrine. Molecular docking and dynamic simulations highlighted strong and stable interactions of the derivatives with critical enzymes, including acetylcholinesterase (AChE) and beta-secretases (BACE1 and BACE2). Compounds 12 and 13, in particular, emerged as the most promising candidates due to their superior stability and binding affinity. These findings underscore the potential of selenium-modified tacrine derivatives as safer and more effective therapeutic agents for Alzheimer’s disease, warranting further experimental validation. Full article

Studying fruit genetic trends, heterosis, and growth traits in pear hybrid progeny provides the foundation for variety breeding. The aim of this research is to reveal the trait performance of the hybrid progeny of Chinese white pear and Western pear and provide a theoretical basis for other breeders to predict the trait performance of their hybrid progeny when selecting Eastern pear and Western pear as parents. Our research team constructed a ‘Yuluxiang’ × ‘Xianghongli’ interspecific hybrid population in 2015, and in 2023, we conducted a two-year investigation of 16 traits in 140 hybrid progeny, including 11 fruit traits and 5 growth traits, and analyzed and compared the genetic variation and heterosis of traits, as well as the correlation between various traits. The results showed that the hybrid progeny was widely segregated for single fruit weight (FW), soluble solid (SS) content, and titratable acid (TA) content and conformed to a normal distribution, with quantitative genetic traits under polygenic control. The highest two-year coefficients of variation for TA were 54.42% in 2023 and 39.17% in 2024. A genetic trend of decreasing FW was observed, which was greatly influenced by the male sex. The ratio of soft soluble flesh to crispy flesh was 1:1, and the gene controlling this trait may be a quality trait controlled by a single gene. The traits that showed transgressive heterosis for two years included fruit longitudinal diameter (FLoD), fruit shape index (FSI), and TA, and those that showed negative heterosis included FW, SS, leaf longitudinal diameter (LLoD), and leaf lateral diameter (LLaD). Correlation analysis indicated that the progeny of crosses in this combination, which had red fruit skin, may also present red early flowering color (EFC) and young leaf color (YLC), reddish brown annual branch color (ABC), and lower FSI, fruit stalk length (FSL), LLaD, and TA. Thus, at the seedling stage, individuals with red-colored fruit may be screened by observing the color of young leaves and young stems and the lateral diameter of the leaves. Principal component analysis showed that among the 16 traits included in six principal components, peel color (PC), FLoD, 2024SS, fruit tape (FT), and FSI were the main factors causing differences in fruit phenotypes. This study systematically elucidated the genetic trends of agronomic traits in pears and will provide a theoretical basis for the selection of parents and early selection of hybrid progeny in pear hybrid breeding. Full article

Chloroderivatives of phenoxyacetic acid are a group of compounds commonly used as plant protection products. Differences in the molecular structure of these compounds are related to varying substitution and the number of chlorine atoms in the aromatic ring. Different molecular structures may affect the activity of these compounds, their physicochemical properties, as well as their toxicity and biological effects. A group of 6 chemical compounds derived from phenoxyacetic acid was tested. The molecular structure was analysed using spectroscopic methods (FTIR, FTRaman, UV-VIS, ¹HNMR, ¹³CNMR) and quantum chemical computational methods (DFT). The reactivity of the tested compounds was determined using DFT calculations and experimentally in reaction with a hydroxyl radical. The electronic charge distribution of NBO, CHelpG and ESP was analysed and aromaticity indices were calculated for theoretically modeled structures and structures examined by X-ray diffraction (data obtained from the CSD database). Phenoxyacetic acid derivatives were tested for antimicrobial activity on soil bacterial strains. Cytotoxicity tests were performed on normal human skin fibroblasts (BJ CRL-2522) and the human prostate cancer cell line (DU-145 HTB-81). The purpose of this study was to investigate the relationship between the molecular structure of phenoxyacetic acid derivatives and their reactivity and biological activity. Full article

Benchmark data are reported for a solid-state laser-based near-infrared spectrometer designed for noninvasive measurements in human skin. These data were obtained using a set of aqueous phantoms composed of polystyrene beads, triton X-100, saline, and glucose. The performance of this prototype solid-state laser platform was compared to parallel results obtained with a Fourier-transform (FT) spectrometer. The fundamental spectroscopic performances of the two spectrometer systems were quantified by an analysis of 100% lines determined by ratioing back-to-back spectra collected over time for each phantom. Root mean square (RMS) noise levels were computed for each dataset and the median RMS noise levels were 327.8 µAU and 667.2 µAU for the FT spectrometer and prototype laser platform, respectively. The analytical utility of the solid-state laser platform was assessed through a series of leave-one-phantom-out partial least squares analyses. Results for the laser prototype data included a standard error of cross validation (SECV) of 7.82 mg/dL for an optimized PLS model with 10 factors over a spectral range of 1401–2238 nm. This compares favorably with the results from the FT spectrometer of an SECV of 6.62 mg/dL with 8 factors and a spectral range of 1551–2378 nm. The additional two PLS factors for the laser prototype were shown to be a consequence of its higher spectral noise. Selectivity of these PLS models was demonstrated by comparing models associated with correct and random glucose assignments to each spectrum. Overall, these findings benchmark the analytical utility of this solid-state laser prototype. Full article

Hazelnut processing generates a variety of by-products, including skins, shells, and defatted (DFT) flour, which contain valuable bioactive compounds. These by-products are rich in polyphenols, fibers, and other molecules that are suitable for incorporation into nutraceutical and cosmetic products. The efficiency of three natural deep eutectic solvents (NADES), such as betaine/sorbitol/water (BS), fructose/lactic acid/water (FL), and fructose/glycerol/water (FG) was compared with a control (C) extractant (ethanol/water). These NADES were combined with two extraction techniques: a conventional method involving heat and magnetic stirring, and ultra-sound-assisted extraction (US). The free radical scavenging capacity (FRC), total phenolic content (TPC), and the polyphenolic profile (HPLC) were evaluated. BS NADES exhibited superior efficiency for the extraction from the skin and shell, while FL was optimal for defatted flour. Although the skin is the least abundant hazelnut processing by-product, it exhibited the highest polyphenol content and antiradical activity, indicating potential for cosmetic applications. The suitability of DFT flour, skin, and the residual panel of extracts for thermochemical and biochemical conversion processes was investigated. Some of the materials were found to be conducive to thermochemical conversion, while others were suitable for anaerobic digestion. Full article

Salvia haenkei (SH-Haenkenium^®), a native plant of Bolivia, is known as strong inhibitor of senescence and recently exploited in wound healing and for its potential anti-inflammatory properties. Hyaluronan at high and low molecular weight (HCC), explored in diverse cell models, and recently used in clinical practice, showed beneficial effects in dermo aesthetic and regenerative injective treatments. In this research work a novel formulation based on HCC coupled SH was tested for its potentiality in counteracting dermal injury. In vitro wound healing has been used to demonstrate HCC + SH capacity to improve keratinocytes migration respects the sole HCC, supported also by positive modulation of remodeling and integrity biomarkers. In addition, an in vitro dehydration test showed its ability to defend the skin from dryness. Moreover, an in vitro inflammation model (with lipopolysaccharides derived from E. coli) was used to assess molecular fingerprint of the pathological model and compare the cell response after treatments. Inflammatory biomarkers (e.g., KRT6, TLR-4 and NF-κB) and specific cytokines (e.g., IL-6, IL-22, IL-23) proved the effect of HCC + SH, in reducing inflammatory mediators. A more complex model, 3D-FT skin, was used to better resemble an in vivo condition, and confirmed the efficacy of novel formulations to counteract inflammation. All results trigger the interest in the novel formulation based on SH extract and hyaluronan complexes for its potential efficacy as natural anti-inflammatory agent for damaged skin, for its healing and regenerative properties. Full article

The Thymus vulgaris and Origanum vulgare essential oils (contained thymol and carvacrol in a range of 35–80%) are used in various products in the fields of medicine, cosmetics, and foods. Molecular hybridization between benzothiazole (BT) and phenolic monoterpenoids is a promising method for the development of biologically active compounds. New benzothiazole–monoterpenoid hybrids were synthesized through a regioselective α-amidoalkylation reaction of thymol and carvacrol with high yields (70–96%). This approach is both simple and cost-effective, employing easily accessible and inexpensive reagents to produce target molecules. The structure of the synthesized compounds was characterized spectrally using ¹H-, ¹³C-NMR, FT-IR, and HRMS data. The newly obtained compounds are structural analogues of the UVB filter PBSA, which is used in cosmetics. The spectral properties of the aromatic products thymol hybrid (2-(4-hydroxy-5-isopropyl-2-methylphenyl)benzo[d]thiazole) and carvacrol hybrid (2-(4-hydroxy-2-isopropyl-5-methylphenyl)benzo[d]thiazole) were successfully examined, using a validated spectrophotometric method. SPF values varied from 31 to 36, compared to the PBSA (30), and were observed at concentrations of 1–0.25 mM. 2-Hydroxyphenylbenzothiazoles are known antimicrobial and antioxidant agents that have potential applications in the food industry and cosmetics as preservatives and antioxidants. In this context, antimicrobial activity of the hybrid compounds was evaluated using the agar diffusion method against E. coli, S. aureus, P. aeruginosa, and C. albicans. Compounds of methyl-2-(4-hydroxy-2-isopropyl-5-methylphenyl)benzo[d]thiazole-3(2H)-carboxylate containing carvacrol fragments showed high activity against Staphylococcus aureus ATCC 25923 (with 0.044 μmol content). The radical scavenging activity was determined using ABTS and DPPH assays, the highest activity was exhibited by the thymol hybrids ethyl-2-(4-hydroxy-5-isopropyl-2-methylphenyl)benzo[d]thiazole-3(2H)-carboxylate (IC₅₀—133.70 ± 10 µM) and methyl-2-(4-hydroxy-5-isopropyl-2-methylphenyl)benzo[d]thiazole-3(2H)-carboxylate (IC₅₀—157.50 ± 10 µM), defined by ABTS. The aromatic benzothiazole–monoterpenoid hybrids are classified using in silico analyses as non-mutagenic, with low toxicity, and they are non-irritating to the skin. These compounds were identified as new hit scaffolds for multifunctional molecules in cosmetics. Full article

Background: Melanoma is the most aggressive and lethal skin cancer that affects thousands of people worldwide. Ruthenium complexes have shown promising results as cancer chemotherapeutics, offering several advantages over platinum drugs, such as potent efficacy, low toxicity, and less drug resistance. Additionally, anthraquinone derivatives have broad therapeutic applications, including melanoma. Objectives: Thus, two new ruthenium complexes with 1-hydroxy-9,10-anthraquinone were obtained: trans-[Ru(HQ)(PPh₃)₂(bipy)]PF₆ (1) and cis-[RuCl₂(HQ)(dppb)] (2), where HQ = 1-hydroxy-9,10-anthraquinone, PPh₃ = triphenylphospine, bipy = 2,2′-bipyridine, PF₆ = hexafluorophosphate, and dppb = 1,4-bis(diphenylphosphine)butane. Methods: The complexes were characterized by infrared (IR), UV–vis, ¹H, ¹³C{¹H}, and ³¹P{¹H} NMR spectroscopies, molar conductivity, cyclic voltammetry, and elemental analysis. Furthermore, density functional theory (DFT) calculations were performed. Results: Compound (2) was determined by single-crystal X-ray diffraction, which confirms the bidentate coordination mode of HQ through the carbonyl and phenolate oxygens. Additionally, DNA-binding experiments yielded constants of 10⁵ M⁻¹ (Kb = 6.93 × 10⁵ for (1) and 1.60 × 10⁵ for (2)) and demonstrate that both complexes can interact with DNA through intercalation, electrostatic attraction, or hydrogen bonding. Conclusions: The cytotoxicity profiles of the compounds were evaluated in human melanoma cell lines (SK-MEL-147, CHL-1, and WM1366), revealing greater cytotoxic activity for (1) on the CHL-1 cell line with an IC₅₀ of 14.50 ± 1.09 µM. Subsequent studies showed that (1) inhibits the proliferation of CHL-1 cells and induces apoptosis, associated at least in part with the pro-oxidant effect and cell cycle arrest at the G1/S transition. Full article

Wound healing stands as a paramount therapeutic pursuit, imposing significant challenges on healthcare, particularly for vulnerable populations. Cedrus brevifolia, a species endemic to Cyprus, thrives in the Tripylos region, commonly known as Cedar Valley, within the Paphos forest. Despite its endemism, this species exhibits negligible genetic divergence from its Mediterranean related species. This study aims to investigate the potential of C. brevifolia resin and bark extracts in promoting wound healing in a mouse model. Previous in vitro investigations have elucidated the antioxidant and anti-inflammatory potential of extracts and isolates derived from the title plant, warranting further exploration in an in vivo setting. This experimental design employed 40 male SKH-hr2 black and brown mice aged 2–4 months. Wounds measuring 1 cm² were meticulously induced in the anesthetized mice and the potential healing effect of the herbal hydrogel formulations was evaluated. The healing potential of the C. brevifolia extracts was rigorously assessed through the daily application of gel formulations containing resin concentrations of 5% and 10% w/w, alongside sapwood and heartwood extracts at concentrations of 0.5% and 1% w/w. The evaluation of the treatments encompassed a multifaceted approach, incorporating clinical observations, skin biophysical parameter assessments utilizing an Antera 3D camera, and FT-IR spectroscopy, in addition to histopathological examination. The chemical compositions were also investigated through NMR and bio-guided isolation. The most prominent herbal hydrogel preparation proved to be the 10% resin, followed by the sapwood at 1%. The chemical analysis unveiled abietic acid, manool, and lariciresinol derivatives that potentially contributed to the observed results. Bridging the gap between in vitro observations and in vivo outcomes attempts to shed light on the potential therapeutic benefits of C. brevifolia hydrogels in wound care. Full article

Anthocyanins, typical polyphenol compounds in grape skin, have attracted increasing interest due to their health-promoting properties. In this body of work, five representative anthocyanins (Cy-3-O-glc, Dp-3-O-glc, Pn-3-O-glc, Mv-3-O-glc, and Pt-3-O-glc) were studied using the density functional theory (DFT) to elucidate structure–radical scavenging activity in the relationship and the reaction path underlying the radical-trapping process. Based on thermodynamic parameters involved in HAT, SET-PT, and SPLET mechanisms, along with the structural attributes, it was found that the C4′ hydroxyl group mainly contributes to the radical scavenging activities of the investigated compounds. Pt-3-O-glc exhibits a good antioxidant capacity among the five compounds. The preferred radical scavenging mechanisms vary in different phases. For the Pt-3-O-glc compound, the calculations indicate the thermodynamically favoured product is benzodioxole, rather than o-quinone, displaying considerably reduced energy in double HAT mechanisms. Additionally, the thermodynamic and kinetic calculations indicate that the reaction of ^•OH into the 4′-OH site of Pt-3-O-glc has a lower energy barrier (7.6 kcal/mol), a higher rate constant (5.72 × 10⁹ M⁻¹ s⁻¹), and exhibits potent ^•OH radical scavenging properties. Molecular docking results have shown the strong affinity of the studied anthocyanins with the pro-oxidant enzyme xanthine oxidase, displaying their significant role in inhibiting ROS formation. Full article

Phycocyanin (PC) is a naturally occurring green pigment in Spirulina. It was extracted by ultrasonic extraction using green technology, and its structure was studied using IR- and NMR-spectroscopy. Spectral data confirmed the PC structure. This study also involves an in silico assessment of the diverse applications of green pigment PC. Utilizing QSAR, PreADME/T, SwissADME, and Pro-Tox, this study explores the safety profile, pharmacokinetics, and potential targets of PC. QSAR analysis reveals a favorable safety profile, with the parent structure and most metabolites showing no binding to DNA or proteins. PreADME/T indicates low skin permeability, excellent intestinal absorption, and medium permeability, supporting oral administration. Distribution analysis suggests moderate plasma protein binding and cautious blood–brain barrier permeability, guiding formulation strategies. Metabolism assessments highlight interactions with key cytochrome P450 enzymes, influencing drug interactions. Target prediction analysis unveils potential targets, suggesting diverse therapeutic effects, including cardiovascular benefits, anti-inflammatory activities, neuroprotection, and immune modulation. Based on the in silico analysis, PC holds promise for various applications due to its safety, bioavailability, and potential therapeutic benefits. Experimental validation is crucial to elucidate precise molecular mechanisms, ensuring safe and effective utilization in therapeutic and dietary contexts. DFT calculations, including geometry optimization, MEP analysis, HOMO-LUMO energy surface, and quantum reactivity parameters of the PC compound, were obtained using the B3LYP/6–311G(d,p) level. This integrated approach contributes to a comprehensive understanding of PC’s pharmacological profile and informs future research directions. Full article

The O₂ dissociative adsorption serves as a pivotal criterion for assessing the efficacy of oxygen reduction catalysts. We conducted a systematic investigation into O₂ dissociative adsorption on the Pt-skin Pt₃Cu(111) surface by means of the density functional theory (DFT). The computational findings reveal that the O₂ adsorption on Pt-skin Pt₃Cu(111) surface exhibits comparatively lower stability when contrasted with that on the Pt(111) surface. For O₂ dissociation, two paths have been identified. One progresses from the t-f-b state towards the generation of two oxygen atoms situated within nearest-neighbour hcp sites. The other commences from the t-b-t state, leading to the generation of two oxygen atoms occupying nearest-neighbour fcc sites. Moreover, the analysis of the energy barrier associated with O₂ dissociation indicates that O₂ on the Pt-skin Pt₃Cu(111) surface is more difficult to dissociate than on the Pt(111) surface. This study can offer a valuable guide for the practical application of high-performance oxygen reduction catalysts. Full article

Skin tissue injuries necessitate particular care due to associated complex healing mechanisms. Current investigations in the domain of tissue engineering and regenerative medicine are focused on obtaining novel scaffolds adapted as potential delivery systems to restore lost tissue functions and properties. In this study, we describe the fabrication and evaluation of a novel 3D scaffold structure based on collagen and silk sericin (CollSS) enriched with microcapsules containing natural compounds, curcumin (C), and/or quercetin (Q). These 3D composites were characterized by FT-IR spectroscopy, water uptake, in vitro collagenase degradation, and SEM microscopy. Furthermore, they were biologically evaluated in terms of biocompatibility, cell adhesion, anti-inflammatory, and antioxidant properties. All tested materials indicated an overall suitable biocompatibility, with the best results obtained for the one containing both flavonoids. This study suggests the cumulative beneficial effect of C and Q, encapsulated in the same composite, as a potential non-invasive therapeutic strategy for skin tissue regeneration in patients suffering from chronic wounds. Full article

This study provides a comprehensive computational exploration of the inhibitory activity and metabolic pathways of 8-methoxypsoralen (8-MP), a furocoumarin derivative used for treating various skin disorders, on cytochrome P450 (P450). Employing quantum chemical DFT calculations, molecular docking, and molecular dynamics (MD) simulations analyses, the biotransformation mechanisms and the active site binding profile of 8-MP in CYP1B1 were investigated. Three plausible inactivation mechanisms were minutely scrutinized. Further analysis explored the formation of reactive metabolites in subsequent P450 metabolic processes, including covalent adduct formation through nucleophilic addition to the epoxide, 8-MP epoxide hydrolysis, and non-CYP-catalyzed epoxide ring opening. Special attention was paid to the catalytic effect of residue Phe268 on the mechanism-based inactivation (MBI) of P450 by 8-MP. Energetic profiles and facilitating conditions revealed a slight preference for the C4′=C5′ epoxidation pathway, while recognizing a potential kinetic competition with the 8-OMe demethylation pathway due to comparable energy demands. The formation of covalent adducts via nucleophilic addition, particularly by phenylalanine, and the generation of potentially harmful reactive metabolites through autocatalyzed ring cleavage are likely to contribute significantly to P450 metabolism of 8-MP. Our findings highlight the key role of Phe268 in retaining 8-MP within the active site of CYP1B1, thereby facilitating initial oxygen addition transition states. This research offers crucial molecular-level insights that may guide the early stages of drug discovery and risk assessment related to the use of 8-MP. Full article