Background: Melanoma patients stop responding to targeted therapies mainly due to mitogen activated protein kinase (MAPK) pathway re-activation, phosphoinositide 3 kinase/the mechanistic target of rapamycin (PI3K/mTOR) pathway activation or stromal cell influence. The future of melanoma treatment lies in combinational approaches. To address this, our in vitro study evaluated if lower concentrations of Celecoxib (IC₅₀ in nM range) could still preserve the chemopreventive effect on melanoma cells treated with trametinib. Materials and Methods: All experiments were conducted on SK-MEL-28 human melanoma cells and BJ human fibroblasts, used as co-culture. Co-culture cells were subjected to a celecoxib and trametinib drug combination for 72 h. We focused on the evaluation of cell death mechanisms, melanogenesis, angiogenesis, inflammation and resistance pathways. Results: Low-dose celecoxib significantly enhanced the melanoma response to trametinib. The therapeutic combination reduced nuclear transcription factor (NF)–kB (p < 0.0001) and caspase-8/caspase-3 activation (p < 0.0001), inhibited microphthalmia transcription factor (MITF) and tyrosinase (p < 0.05) expression and strongly down-regulated the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway more significantly than the control or trametinib group (p < 0.0001). Conclusion: Low concentrations of celecoxib (IC₅₀ in nM range) sufficed to exert antineoplastic capabilities and enhanced the therapeutic response of metastatic melanoma treated with trametinib.

Chronic wounds are a major health problem, affecting millions of people worldwide. Resistance to treatment is frequently observed, requiring an extension of the wound healing time, and improper care can lead to more problems in patients. Smart wound dressings that provide a controlled drug release can significantly improve the healing process. In this paper, alginate beads with white lily leaf extract were prepared and tested for chronic wound healing. The obtained beads were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Also, the efficiency of extract encapsulation in alginate was determined as being of. The obtained hydrogel was tested on two normal human cell lines, respectively, dermal fibroblasts (BJ-CRL-2522-ATCC) and endothelial cells (human umbilical vein endothelial cells—HUVEC 2). The longer release of bioactive compounds from plant extract loaded in the alginate hydrogel resulted in more effective wound closure, compared to the extract alone, and scar formation, compared to the alginate hydrogel. Therefore, the effect of the white lily extract in combination with that of sodium alginate hydrogel improves the biological activity of the alginate hydrogel and increases the wound healing properties of the alginate.

Alzheimer’s disease (AD) is known as the primary and most common cause of dementia in the middle-aged and elderly population worldwide. Chemical analyses of B. pendula leaf extract (BPE), performed using spectrophotometric and chromatographic methods (LC/MS), revealed high amounts of polyphenol carboxylic acids (gallic, chlorogenic, caffeic, trans-p-coumaric, ferulic, and salicylic acids), as well as flavonoids (apigenin, luteolin, luteolin-7-O-glucoside, naringenin, hyperoside, quercetin, and quercitrin). Four groups of Wistar rats were used in this experiment (n = 7/group): control (untreated), Aβ_1-42 (2 μg/rat intracerebroventricular (i.c.v.), Aβ_1-42 + BPE (200 mg/Kg b.w.), and DMSO (10 μL/rat). On the first day, one dose of Aβ_1-42 was intracerebroventricularly administered to animals in groups 2 and 3. Subsequently, BPE was orally administered for the next 15 days to group 3. On the 16th day, behavioral tests were performed. Biomarkers of brain oxidative stress Malondialdehyde (MDA), (Peroxidase (PRx), Catalase (CAT), and Superoxid dismutase (SOD) and inflammation (cytokines: tumor necrosis factor -α (TNF-α), Interleukin 1β (IL-1β), and cyclooxygenase-2 (COX 2)) in plasma and hippocampus homogenates were assessed. Various protein expressions (Phospho-Tau (Ser404) (pTau Ser 404), Phospho-Tau (Ser396) (pTau Ser 396), synaptophysin, and the Nuclear factor kappa B (NFkB) signaling pathway) were analyzed using Western blot and immunohistochemistry in the hippocampus. The results show that BPE diminished lipid peroxidation and neuroinflammation, modulated specific protein expression, enhanced the antioxidant capacity, and improved spontaneous alternation behavior, suggesting that it has beneficial effects in AD.

Development of cocrystals through crystal engineering is a viable strategy to formulate poorly water-soluble active pharmaceutical ingredients as stable crystalline solid forms with enhanced bioavailability. This study presents a controlled cocrystallization process by cooling for the 1:1 cocrystal of Ketoconazole, an antifungal class II drug with the Fumaric acid coformer. This was successfully set up following the meta-stable zone width determination in acetone–water 4:6 (V/V) and pure ethanol. Considering the optimal crystallization data, laboratory scale-up processes were carried out at 1 g batch size, efficiently delivering the cocrystal in high yields up to 90% pure and single phase as revealed by powder X-ray diffraction. Biological assays in vitro showed improved viability and oxidative damage of the cocrystal over Ketoconazole on human dermal fibroblasts and hepatocarcinoma cells; in vivo, on Wistar rats, the cocrystal increased oral Ketoconazole bioavailability with transient minor biochemical transaminases increases and without histological liver alterations. Locally on Balb C mice, it induced no epicutaneuous sensitization. A molecular docking study conducted on sterol 14α-demethylase (CYP51) enzyme from the pathogenic yeast Candida albicans revealed that the cocrystal interacts more efficiently with the enzyme compared to Ketoconazole, indicating that the coformer enhances the binding affinity of the active ingredient.

(1) Background: Photodynamic therapy (PDT) involves the selective killing of tumor cells by the generation of reactive oxygen species using a photosensitizer (PS) activated by irradiation. In melanoma, PDT efficiency is altered by several mechanisms, such as the presence of melanin and melanosomes and pro-survival pathways mediated by transcription factors such as: AP-1 (activator protein), MITF (microphthalmia inducible transcription factor), HIF1α (hypoxia inducible factor), and NF-kB (nuclear factor kappa B). The study aimed to investigate the anti-melanoma effects of PDT mediated by meso-5,10,15,20-tetrakis-(4-hydroxyphenyl)-porphyrin (THPP) as a photosensitizer. (2) Methods: Cocultures of melanoma, two human, WM35 and M1–15, and murine B16-F10, with endothelial cells, were used. Cytotoxicity, oxidative damage, angiogenesis markers, and melanogenesis were assessed using colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, and Western blotting. (3) Results: The maximal killing efficiency of PDT was reached in WM35, followed by M1–15, and then B16-F10, and it occurred through both apoptosis and necrosis. Although constitutive pigmentation diminished the PDT efficiency, de novo melanogenesis exhibited no protection. PDT increased TNFα, and inhibited NFkB, MITF, HIF1α, and AP1, leading to inflammation and angiogenesis markers’ inhibition. (4) Conclusions: THPP-mediated PDT efficiently induced cell death through apoptosis, necrosis, and the inhibition of pro-survival pathways mediated by NFkB, AP1, HIF1α, and MITF in the melanoma coculture models.