Phytochemical and Nutraceutical Screening of Ethanol and Ethyl Acetate Phases of Romanian Galium verum Herba (Rubiaceae).

Galium species are used worldwide for their antioxidant, antibacterial, antifungal, and antiparasitic properties. Although this plant has demonstrated its antitumor properties on various types of cancer, its biological activity on cutaneous melanoma has not been established so far. Therefore, the present study was designed to investigate the phytochemical profile of two extracts of G. verum L. herba (ethanolic and ethyl acetate) as well as the biological profile (antioxidant, antimicrobial, and antitumor effects) on human skin cancer. The extracts showed similar FT-IR phenolic profiles (high chlorogenic acid, isoquercitrin, quercitrin, and rutin), with high antioxidant capacity (EC50 of ethyl acetate phase (0.074 ± 0.01 mg/mL) > ethanol phase (0.136 ± 0.03 mg/mL)). Both extracts showed antimicrobial activity, especially against Gram-positive Streptococcus pyogenes and Staphylococcus aureus bacilli strains, the ethyl acetate phase being more active. Regarding the in vitro antitumor test, the results revealed a dose-dependent cytotoxic effect against A375 melanoma cell lines, more pronounced in the case of the ethyl acetate phase. In addition, the ethyl acetate phase stimulated the proliferation of human keratinocytes (HaCaT), while this effect was not evident in the case of the ethanolic phase at 24 h post-stimulation. Consequently, G. verum l. could be considered a promising phytocompound for the antitumor approach of cutaneous melanoma.

Correlations on Phenolic Screening Related to In Vitro and In Ovo Assessment of Ocimum basilicum L. Hydro-Alcoholic Extracts Used as Skin Active Ingredient.

The current study was aimed to evaluate the phenolic composition parameters of two hydro-alcoholic extracts of Ocimum basilicum L. (OB) obtained from the aerial part (without leaves) and leaves, in order to determine their contribution to the antioxidant activity (AOA). Both hydro-alcoholic extracts have proven to be rich in polyphenolic compounds, flavonoids, flavonols and tannins. Therefore, the leaves' extracts reveal an inhibition percentage of 89%, almost comparable with the standard reference (95%). To complete the toxicological profile, the study also assessed the potential cytotoxicity of basil hydro-alcoholic extracts on immortalized human keratinocytes (HaCaT), skin human fibroblasts (1BR3), mice epidermis (JB6Cl41-5a) and primary human melanocytes (HEMa) cells, correlated to A375 antitumor in vitro activity. The extracts did not induce significant cytotoxic effect on any of the selected normal cell lines but showed relevant activity on A375 cells. Considering the low values obtained regarding the irritative effects in the chorionallantoic membrane of the egg on blood vessels, we can emphasize that both extracts can be considered as biocompatible ingredients. Regarding the potential activity of hydro-alcoholic extracts on human skin, the decrease of erythema values after the application of extracts was a relevant observation which indicates the anti-inflammatory potential of Ocimum basilicum L.

Synthesis, characterization, and in vitro-in ovo toxicological screening of silibinin fatty acids conjugates as prodrugs with potential biomedical applications.

Silibinin (SIL), the most active phytocompound from Silybum marianum (L.), exerts many biological effects but has low stability and bioavailability. To overcome these drawbacks, the current research proposed the synthesis of silibilin oleate (SIL-O) and silibilin linoleate (SIL-L) derivatives as prodrugs with potentially optimized properties for biomedical applications, and the establishment of their in vitro-in ovo safety profiles. The physicochemical characterization of the obtained compounds using density functional theory (DFT) calculations, and Raman and 1H liquid-state nuclear magnetic resonance (NMR) spectroscopy confirmed the formation of SIL-O and SIL-L complexes. Computational predictions revealed that these lipophilic derivatives present a lower drug-likeness score (-29.96 for SIL-O and -23.55 for SIL-L) compared to SIL, but an overall positive drug score (0.07) and no risk for severe adverse effects. SIL-O and SIL-L showed no cytotoxicity or impairment in cell migration at low concentrations, but at the highest concentration (100 µM), they displayed distinct toxicological profiles. SIL-L was more cytotoxic (on cardiomyoblasts - H9c2(2-1), hepatocytes - HepaRG, and keratinocytes - HaCaT) than SIL-O or SIL, significantly inhibiting cell viability (< 60%), altering cellular morphology, reducing cell confluence (< 70%), and inducing prominent apoptotic-like nuclear features. At the concentration of 100 µM, SIL-O presented an irritation score (IS) of 0.61, indicating a lack of irritant effect on the chorioallantoic membrane (CAM), while SIL-L was classified as a slight irritant with an IS of 1.99. These findings outline a more favorable in vitro and in ovo biocompatibility for SIL-O compared to SIL-L, whose applications are dosage-limited due to potential toxicity.

Time-to-Treatment Delays and Their Prognostic Implications in Pharyngeal Cancer-An Exploratory Analysis in Western Romania.

BACKGROUND: Diagnosis and treatment for pharyngeal cancer are decisive in determining prognosis. Diagnosis delays are frequent, representing a significant cause of avoidable mortality, and an important factor in subpar survival across the continuous HNC care delivery. METHODS: The present study represents a retrospective analysis of medical records from Western Romania, which included 180 patients, to evaluate the impact of time-to-treatment delay on patients diagnosed with pharyngeal cancer. The data analyses were performed using the Kaplan-Meier method R (version 3.6.3) packages, including tidyverse, final-fit, mcgv, survival, stringdist, janitor, and Hmisc. RESULTS: The mean days from diagnosis until the end of treatment were higher for the nasopharynx group. Cox regression analysis regarding diagnosis to treatment duration categories showed an increased risk mortality by 3.11 times (95%CI: 1.51-6.41, p = 0.0021) with a Harrell's C-index of 0.638 (95%CI: 0.552-0.723). The hypopharynx and oropharynx locations increased risk mortality by 4.59 (95%CI: 1.55-13.55) and 5.49 times (95%CI: 1.79-16.81) compared to the nasopharynx location. CONCLUSIONS: The findings of this study led to the conclusion that it seems there is a trend of mortality risk for oropharynx and hypopharynx cancers due to delays in the time to treatment over 70 days, standing as a basis for further research as there is an imperative need for prospective multicenter studies.

New Insights Concerning Phytophotodermatitis Induced by Phototoxic Plants.

The present review explores the underlying mechanisms of phytophotodermatitis, a non-immunologic skin reaction triggered by certain plants followed by exposure to ultraviolet radiation emitted by sunlight. Recent research has advanced our understanding of the pathophysiology of phytophotodermatitis, highlighting the interaction between plant-derived photosensitizing compounds (e.g., furanocoumarins and psoralens) and ultraviolet light leading to skin damage (e.g., erythema, fluid blisters, edema, and hyperpigmentation), identifying these compounds as key contributors to the phototoxic reactions causing phytophotodermatitis. Progress in understanding the molecular pathways involved in the skin's response to these compounds has opened avenues for identifying potential therapeutic targets suitable for the management and prevention of this condition. The review emphasizes the importance of identifying the most common phototoxic plant families (e.g., Apiaceae, Rutaceae, and Moraceae) and plant species (e.g., Heracleum mantegazzianum, Ruta graveolens, Ficus carica, and Pastinaca sativa), as well as the specific phytochemical compounds responsible for inducing phytophototoxicity (e.g., limes containing furocoumarin have been linked to lime-induced photodermatitis), underscoring the significance of recognizing the dangerous plant sources. Moreover, the most used approaches and tests for accurate diagnosis such as patch testing, Wood's lamp examination, or skin biopsy are presented. Additionally, preventive measures such as adequate clothing (e.g., long-sleeved garments and gloves) and treatment strategies based on the current knowledge of phytophotodermatitis including topical and systemic therapies are discussed. Overall, the review consolidates recent findings in the field, covering a diverse array of phototoxic compounds in plants, the mechanisms by which they trigger skin reactions, and the implications for clinical management. By synthesizing these insights, we provide a comprehensive understanding of phytophotodermatitis, providing valuable information for both healthcare professionals and researchers working to address this condition.

Recent Updates Regarding the Antiproliferative Activity of Galium verum Extracts on A375 Human Malignant Melanoma Cell Line.

The biological activity of Galium verum herba was exerted on various tumor cell lines with incredible results, but their potential effect on malignant melanoma has not been established yet. Therefore, the current study was structured in two directions: (i) the investigation of the phytochemical profile of diethyl ether (GvDEE) and butanol (GvBuOH) extracts of G. verum L. and (ii) the evaluation of their biological profile on A375 human malignant melanoma cell line. The GvDEE extract showed an FT-IR profile different from the butanol one, with high antioxidant capacity (EC50 of GvDEE = 0.12 ± 0.03 mg/mL > EC50 of GvBuOH = 0.18 ± 0.05 mg/mL). The GvDEE extract also showed antimicrobial potential, especially against Gram-positive bacteria strains, compared to the butanol extract, which has no antimicrobial activity against any bacterial strain tested. The results regarding the antitumor potential showed that both extracts decreased A375 cell viability largely (69% at a dose of 55 µg/mL of the GvDEE extract). Moreover, both extracts induce nuclear fragmentation by forming apoptotic bodies and slight chromatin condensation, which is more intense for GvDEE. Considering the results, one can state that the Galium verum herba possesses antitumor effects on the A375 human malignant melanoma cell line, a promising phytocompound for the antitumor approach to skin cancer.

Stability Profile and Clinical Evaluation of an Innovative Hydrogel Containing Polymeric Micelles as Drug Delivery Systems with Oregano Essential Oil against Fibroepithelial Polyps.

Skin tags, also known as fibroepithelial polyps (FPs) or acrochordons, are soft, pigmented excrescences, with a prevalence of 50-60% in the population, occurring especially in the fourth decade of life. To date, FPs have been efficiently eliminated using minimum invasive methods such as surgical removal, cauterization, laser irradiation, and cryosurgery. Over-the-counter treatments are also of interest for patients due to their non-invasive character, but their clinical efficiency has not been clearly demonstrated. This study was designed in order to evaluate the efficacy of a modern-pharmaceutical-formulation-type poloxamer-based binary hydrogel, having Origanum vulgare L. essential oil (OEO-PbH) as an active ingredient in the management of FPs. The formulation has been shown to possess good qualities in terms of stability and sterility. Non-invasive measurements revealed changes in some physiological skin parameters. An increase in transepidermal water loss (TEWL) and erythema index was noted, while skin surface water content (SWC) decreased during eight weeks of treatment. The macroscopic evaluation revealed that the FPs dried and shrunk after topical treatment with OEO-PbH. Clinically, patients presented a lowering of the number of lesions on the treated area of 20-30% after one month of treatment and around 50% after the second month. Histopathological examination suggests that topical treatment with OEO-PbH may induce histological changes in the epidermis, dermis, and fibrovascular cores of FPs, including a loss of thickness, reduced size and number of blood vessels, and low cellularity. These changes may contribute to the observed reduction in size of FPs after treatment with OEO-PbH.

Biosynthesis of Iron Oxide Nanoparticles: Physico-Chemical Characterization and Their In Vitro Cytotoxicity on Healthy and Tumorigenic Cell Lines.

Iron oxide nanoparticles were synthesized starting from two aqueous extracts based on Artemisia absinthium L. leaf and stems, employing a simplest, eco-friendliness and low toxicity method-green synthesis. The nanoparticles were characterized by powder X-ray diffraction (XRD), Fourier transformed infrared spectroscopy (FT-IR), X-ray fluorescence analysis (XRF), thermal analysis (TG/DSC), and scanning electron microscopy (SEM). Lack of magnetic properties and the reddish-brown color of all the samples confirms the presence of hematite as majority phase. The FTIR bands located at 435 cm-1 and 590 cm-1, are assigned to Fe-O stretching vibration from hematite, confirming the formation of α-Fe2O3 nanoparticles (NPs). The in vitro screening of the samples revealed that the healthy cell line (HaCaT) presents a good viability (above 80%) after exposure to iron oxide NPs and lack of apoptotic features, while the tumorigenic cell lines manifested a higher sensitivity, especially the melanoma cells (A375) when exposed to concentration of 500 µg/mL iron oxide NPs for 72 h. Moreover, A375 cells elicited significant apoptotic markers under these parameters (concentration of 500 µg/mL iron oxide NPs for a contact time of 72 h).

Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT-29 cells.

Recent scientific evidence suggests a link between epigenetic changes (DNA methylation) and tumorigenesis. Moreover, a potential carcinogenic mechanism of cadmium was associated with changes in DNA methylation. In this study we investigated the impact of CdCl2 and CuSO4 aqueous solutions on DNA methylation in HT-29 cells by quantifying DNA methyltransferase (DNMT1, DNMT3A and DNMT3B) mRNA expression. Furthermore, we also studied the cytotoxic and anti-migratory potential of these substances. The results showed a dose-dependent decrease of viable cell percentage following 24 h of exposure (at concentrations of 0.05; 0.2; 1; 10 and 100 µg/ml), and an inhibitory effect on HT-29 cell migration capacity. In addition, RT-qPCR results showed that cadmium acts as a hypomethylating agent by suppressing DNMT expression, whereas copper acts as a hypermethylating compound by increasing DNMT expression. These findings suggest a cytotoxic potential of both cadmium and copper on HT-29 cells and their capacity to induce epigenetic changes.

Design and Assessment of a Polyurethane Carrier Used for the Transmembrane Transfer of Acyclovir.

THE Herpes simplex viruses (HSV-1, HSV-2) are responsible for a wide variety of conditions, from cutaneous-mucosal to central nervous system (CNS) infections and occasional infections of the visceral organs, some of them with a lethal end. Acyclovir is often used intravenously, orally, or locally to treat herpetic infections but it must be administered with caution to patients with kidney disease and to children of early age. The main objectives of this study were to synthesize and evaluate new polyurethane nanoparticles that might be used as proper transmembrane carriers for acyclovir. Polyurethane particles were obtained by a polyaddition process: a mixture of two aliphatic diisocyanates used as organic phase was added to a mixture of butanediol and polyethylene glycol used as aqueous phase. Two different samples (with and without acyclovir, respectively) were synthesized and characterized by UV-Vis spectra in order to assess the encapsulation efficacy and the release profile, FT-IR, DSC, SEM, and SANS for structural characterization, as well as skin irritation tests. Nearly homogeneous samples with particle sizes between 78 and 91 nm have been prepared and characterized revealing a medium tendency to form clusters and a high resistance to heat up to 300 °C. The release profile of these nanoparticles is characteristic to a drug delivery system with a late discharge of the loaded active agents. Very slight increases in the level of transepidermal water loss and erythema were found in a 15-day evaluation on human skin. The results suggest the synthesis of a non-irritative carrier with a high encapsulation efficacy that can be successfully used for the transmembrane transfer of acyclovir.