Eugenol: In Vitro and In Ovo Assessment to Explore Cytotoxic Effects on Osteosarcoma and Oropharyngeal Cancer Cells.

Cancer is a significant health problem worldwide; consequently, new therapeutic alternatives are being investigated, including those found in the vegetable kingdom. Eugenol (Eug) has attracted attention for its therapeutic properties, especially in stomatology. The purpose of this study was to investigate the cytotoxicity of Eug, in vitro, on osteosarcoma (SAOS-2) and oropharyngeal squamous cancer (Detroit-562) cells, as well as its potential irritant effect in ovo at the level of the chorioallantoic membrane (CAM). The data obtained following a 72 h Eug treatment highlighted the reduction in cell viability up to 41% in SAOS-2 cells and up to 37% in Detroit-562 cells, respectively. The apoptotic-like effect of Eug was indicated by the changes in cell morphology and nuclear aspect; the increase in caspase-3/7, -8 and -9 activity; the elevated expression of Bax and Bad genes; and the increase in luminescence signal (indicating phosphatidylserine externalization) that preceded the increase in fluorescence signal (indicating the compromise of membrane integrity). Regarding the vascular effects, slight signs of coagulation and vascular lysis were observed, with an irritation score of 1.69 for Eug 1 mM. Based on these results, the efficiency of Eug in cancer treatment is yet to be clarified.

Rutin bioconjugates as potential nutraceutical prodrugs: An in vitro and in ovo toxicological screening.

Rutin (RUT) is considered one the most attractive flavonoids from a therapeutic perspective due to its multispectral pharmacological activities including antiradical, anti-inflammatory, antiproliferative, and antimetastatic among others. Still, this compound presents a low bioavailability what narrows its clinical applications. To overcome this inconvenience, the current paper was focused on the synthesis, characterization, and toxicological assessment of two RUT bioconjugates obtained by enzymatic esterification with oleic acid (OA) and linoleic acid (LA)-rutin oleate (RUT-O) and rutin linoleate (RUT-L), as flavonoid precursors with improved physicochemical and biological properties. Following the enzymatic synthesis in the presence of Novozyme® 435, the two bioconjugates were obtained, their formation being confirmed by RAMAN and FT-IR spectroscopy. The in vitro and in ovo toxicological assessment of RUT bioconjugates (1-100 µM) was performed using 2D consecrated cell lines (cardiomyoblasts - H9c2(2-1), hepatocytes-HepaRG, and keratinocytes-HaCaT), 3D reconstructed human epidermis tissue (EpiDerm™), and chick chorioallantoic membranes, respectively. The results obtained were test compound, concentration-and cell-type dependent, as follows: RUT-O reduced the viability of H9c2(2-1), HepaRG, and HaCaT cells at 100 µM (to 77.53%, 83.17%, and 78.32%, respectively), and induced cell rounding and floating, as well as apoptotic-like features in the nuclei of all cell lines, whereas RUT-L exerted no signs of cytotoxicity in all cell lines in terms of cell viability, morphology, and nuclear integrity. Both RUT esters impaired the migration of HepaRG cells (at 25 µM) and lack irritative potential (at 100 µM) in vitro (tissue viability >50%) and in ovo (irritation scores of 0.70 for RUT-O, and 0.49 for RUT-L, respectively). Computational predictions revealed an increased lipophilicity, and reduced solubility, drug-likeness and drug score of RUT-O and RUT-L compared to their parent compounds-RUT, OA, and LA. In conclusion, we report a favorable toxicological profile for RUT-L, while RUT-O is dosage-limited since at high concentrations were noticed cytotoxic effects.

Melanin and Melanin-Functionalized Nanoparticles as Promising Tools in Cancer Research-A Review.

Cancer poses an ongoing global challenge, despite the substantial progress made in the prevention, diagnosis, and treatment of the disease. The existing therapeutic methods remain limited by undesirable outcomes such as systemic toxicity and lack of specificity or long-term efficacy, although innovative alternatives are being continuously investigated. By offering a means for the targeted delivery of therapeutics, nanotechnology (NT) has emerged as a state-of-the-art solution for augmenting the efficiency of currently available cancer therapies while combating their drawbacks. Melanin, a polymeric pigment of natural origin that is widely spread among many living organisms, became a promising candidate for NT-based cancer treatment owing to its unique physicochemical properties (e.g., high biocompatibility, redox behavior, light absorption, chelating ability) and innate antioxidant, photoprotective, anti-inflammatory, and antitumor effects. The latest research on melanin and melanin-like nanoparticles has extended considerably on many fronts, allowing not only efficient cancer treatments via both traditional and modern methods, but also early disease detection and diagnosis. The current paper provides an updated insight into the applicability of melanin in cancer therapy as antitumor agent, molecular target, and delivery nanoplatform.

Investigation of Lupeol as Anti-Melanoma Agent: An In Vitro-In Ovo Perspective.

Malignant melanoma (MM) represents the most life-threatening skin cancer worldwide, with a narrow and inefficient chemotherapeutic arsenal available in advanced disease stages. Lupeol (LUP) is a triterpenoid-type phytochemical possessing a broad spectrum of pharmacological properties, including a potent anticancer effect against several neoplasms (e.g., colorectal, lung, and liver). However, its potential as an anti-melanoma agent has been investigated to a lesser extent. The current study focused on exploring the impact of LUP against two human MM cell lines (A375 and RPMI-7951) in terms of cell viability, confluence, morphology, cytoskeletal distribution, nuclear aspect, and migration. Additionally, the in ovo antiangiogenic effect has been also examined. The in vitro results indicated concentration-dependent and selective cytotoxicity against both MM cell lines, with estimated IC50 values of 66.59 ± 2.20 for A375, and 45.54 ± 1.48 for RPMI-7951, respectively, accompanied by a reduced cell confluence, apoptosis-specific nuclear features, reorganization of cytoskeletal components, and inhibited cell migration. In ovo, LUP interfered with the process of angiogenesis by reducing the formation of neovascularization. Despite the potential anti-melanoma effect illustrated in our in vitro-in ovo study, further investigations are required to elucidate the underlying LUP-induced effects in A375 and RPMI-7951 MM cells.

Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity-A Pharmaco-Toxicological Screening.

Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are still debatable and are far from being elucidated. Thus, the present manuscript offers a global perspective on antibiotics in terms of evolution from a historical perspective with an emphasis on the main classes of antibiotics and their adverse effects. It also highlights the connection between antibiotics and microbiota, focusing on the dual role played by antibiotics in tumorigenesis. In addition, using the natural compounds with antibacterial properties as potential alternatives for the classical antibiotic therapy is discussed.

Fe3O4@C Matrix with Tailorable Adsorption Capacities for Paracetamol and Acetylsalicylic Acid: Synthesis, Characterization, and Kinetic Modeling.

In this study Fe3O4@C matrix was obtained by combustion method and used hereafter as adsorbent for paracetamol and acetylsalicylic acid removal from aqueous solutions. The Fe3O4@C matrix was characterized by electronic microscopy, X-ray diffraction, thermal analysis, Fourier-transform infrared spectroscopy, and magnetic measurements. Two kinetic models of pseudo first-order and pseudo-second-order for both paracetamol and acetylsalicylic acid were studied. The experimental data were investigated by Langmuir, Freundlich, and Redlich-Peterson adsorption isotherm models. The adsorption followed the Redlich-Peterson and pseudo-second-order models with correlation coefficients R2 = 0.98593 and R2 = 0.99996, respectively, for the adsorption of paracetamol; for the acetylsalicylic acid, the adsorption followed the Freundlich and pseudo-second-order model, with correlation coefficients R2 = 0.99421 and R2 = 0.99977, respectively. The equilibrium was quickly reached after approximately 1h for the paracetamol adsorption and approximately 2h for acetylsalicylic acid adsorption. According to the Langmuir isotherm, the maximum adsorption capacity of the magnetic matrix was 142.01 mg·g-1 for the retention of paracetamol and 234.01 mg·g-1 for the retention of acetylsalicylic acid. The benefits of using the Fe3O4@C matrix are the low cost of synthesis and its easy and fast separation from solution by using an NdBFe magnet.