Malignant melanoma is one of the most aggressive malignant tumors with unpredictable evolution. Photodynamic therapy has been successfully used as the first line or palliative therapy for the treatment of lung, esophageal, bladder, non melanoma skin and head and neck cancers. However, classical photodynamic therapy has shown some drawbacks that limit its clinical application in melanoma. The most important challenge is to overcome melanoma resistance, due to melanosomal trapping, presence of melanin, enhanced oxidative stress defense, defects in the apoptotic pathways, immune evasion, neoangiogenesis stimulation. In this review we considered: (1) main signaling molecular pathways deregulated in melanoma as potential targets for personalized therapy, including photodynamic therapy, (2) results of the clinical studies regarding the photodynamic therapy of melanoma, especially advanced metastatic stage, (3) progresses made in the design of anti-melanoma photosensitizers (4) inhibition of tumor neoangiogenesis, as well as (5) advantages of the derived therapies like photothermal therapy, sonodynamic therapy. Moreover, the possibility of combined therapeutical regimens, such as photodynamic therapy and immune stimulation or theranostic approaches may increase the potential beneficial role of photodynamic therapy as an adjuvant in melanoma treatment.
Liver fibrosis, a common condition occurring during the evolution of almost all chronic liver diseases, is the consequence of hepatocyte injury that leads to the activation of Kupffer cells and hepatic stellate cells (HSC). Silymarin (Si) is a herbal product widely used for its hepatoprotective potential. Our study aims to investigate the effects of two different doses of Silymarin on a CCl4-induced model of liver fibrosis with a focus on the early stages of liver injury. Fifty Wistar rats were randomly divided into five groups (n=10): control group (sunflower oil twice a week); CMC group (carboxymethyl cellulose five times a week, sunflower oil twice a week); CCl4 group (CCl4 in sunflower oil, by gavage, twice a week); CCl4+Si 50 group (CCl4 twice a week, Silymarin 50 mg/b.w. in CMC five times a week); and CCl4+Si 200 group (similar to the previous group, with Si 200 mg/b.w.). One month after the experiment began we explored hepato-cytolysis (aminotransferases and lactate dehydrogenase), oxidative stress, fibrosis (histological score, hyaluronic acid), markers of HSC activation (transforming growth factor β1 [TGF-β1], and α-smooth muscle actin [α-SMA] expression by western blot) and activation of Kupffer cells by immunohistochemistry. Our data showed that Si 50 mg/b.w. had the capacity of reducing oxidative stress, hepato-cytolysis, fibrosis, activation of Kupffer cells, and the expression of α-SMA and TGF-β1 with better results than Si 200 mg/b.w. Thus, the usual therapeutic dose of Silymarin, administered in the early stages of fibrotic changes is capable of inhibiting the fibrogenetic mechanism and the progression of initial liver fibrosis.
Background The antimicrobial activity of the Equisetum arvense L. extract and the mechanisms involved in the in vitro effects on endothelial vascular cells exposed to hyperosmotic stress were evaluated. Methods Antimicrobial activity was evaluated by disk diffusion method and minimum inhibitory concentration (MIC) determination, and oxidative stress, inflammation, and apoptosis, in pretreatment with Equisetum arvense L., caffeic acid, and cathechin, were quantified. Results The results have shown that Equisetum arvense L. exhibited antibacterial effects only on pathogenic gram-positive cocci. The modulatory activity of Equisetum arvense L. on endothelial cells exposed to hypertonic medium was different and depended on the concentration used. Low concentrations of tested compounds exerted antioxidant effect and diminished the activity of caspase-8 and also increased IκB expression while in high doses, Equisetum arvense L. was prooxidant, induced apoptosis, and decreased IL-6 secretion. Conclusions These experimental findings suggest that Equisetum arvense L. has antibacterial effects on gram-positive cocci and, administered in low dose, may be a new therapeutic approach for diseases associated with hypertonic conditions or oxidative stress and apoptosis.
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