Amphibian skin is a multifunctional organ that plays key roles in defense, breathing, and water balance. In this study, skin secretion samples of the fire salamander (Salamandra salamandra) were separated using RP-HPLC and de novo sequenced using MALDI-TOF MS/MS. Next, we used an in silico platform to screen antioxidant molecules in the framework of density functional theory. One of the identified peptides, salamandrin-I, [M + H]+ = 1406.6 Da, was selected for solid-phase synthesis; it showed free radical scavenging activity against DPPH and ABTS radicals. Salamandrin-I did not show antimicrobial activity against Gram-positive and -negative bacteria. In vitro assays using human microglia and red blood cells showed that salamandrin-I has no cytotoxicity up to the concentration of 100 µM. In addition, in vivo toxicity tests on Galleria mellonella larvae resulted in no mortality at 20 and 40 mg/kg. Antioxidant peptides derived from natural sources are increasingly attracting interest. Among several applications, these peptides, such as salamandrin-I, can be used as templates in the design of novel antioxidant molecules that may contribute to devising strategies for more effective control of neurological disease.

Candida albicans is a major cause of human infections, ranging from relatively simple to treat skin and mucosal diseases to systemic life-threatening invasive candidiasis. Fungal infections treatment faces three major challenges: the limited number of therapeutic options, the toxicity of the available drugs, and the rise of antifungal resistance. In this study, we demonstrate the antifungal activity and mechanism of action of peptides ToAP2 and NDBP-5.7 against planktonic cells and biofilms of C. albicans. Both peptides were active against C. albicans cells; however, ToAP2 was more active and produced more pronounced effects on fungal cells. Both peptides affected C. albicans membrane permeability and produced changes in fungal cell morphology, such as deformations in the cell wall and disruption of ultracellular organization. Both peptides showed synergism with amphotericin B, while ToAP2 also presents a synergic effect with fluconazole. Besides, ToAP2 (6.25 µM.) was able to inhibit filamentation after 24 h of treatment and was active against both the early phase and mature biofilms of C. albicans. Finally, ToAP2 was protective in a Galleria mellonella model of infection. Altogether these results point to the therapeutic potential of ToAP2 and other antimicrobial peptides in the development of new therapies for C. albicans infections. Candida albicans is a fungal species present in the normal human microbiota, colonizing several areas of the body. However, under certain circumstances, this species may become a pathogen, causing diseases that can be life-threatening 1-4. The use of broad-spectrum antibiotics, immune suppression, or changes in the local host environments are examples of situations that may favor the proliferation of C. albicans and the onset of disease 5-8. Moreover, C. albicans ability to thrive in human tissues involves metabolic and morphological changes associated with the expression of different virulence factors 9. C. albicans virulence factors include secretion of enzymes, adhesion to cell surfaces and evasion of the immune system 10,11. Two virulence factors of major clinical importance are the fungal polymorphism and its ability to form biofilms 12-14. C. albicans ability to transit between yeast and filamentous forms is crucial for pathogenesis and both fungal forms are relevant for infection 15. For instance, hyphae have a major role on tissue invasion, whereas the yeast morphology facilitates fungal dispersion 16. The different fungal morphologies are also important for the formation of C. albicans biofilms 17. Living in biofilms confers to the microorganisms several advantages, when compared to the planktonic lifestyle, including protection against immune cells, increased resistance to antimicrobials agents and other chemical, physical and environmental stressors 18,19 .

Background Self-emulsifying drug delivery systems (SEDDSs) have attracted attention because of their effects on solubility and bioavailability of lipophilic compounds. Herein, a SEDDS loaded with lycopene purified from red guava (nanoLPG) was produced. The nanoemulsion was characterized using dynamic light scattering (DLS), zeta potential measurement, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), lycopene content quantification, radical scavenging activity and colloidal stability in cell culture medium. Then, in vivo toxicity and tissue distribution in orally treated mice and cytotoxicity on human prostate carcinoma cells (DU-145) and human peripheral blood mononuclear cells (PBMC) were evaluated. Results NanoLPG exhibited physicochemical properties with a size around 200 nm, negative zeta-potential, and spherical morphology. The size, polydispersity index, and zeta potential parameters suffered insignificant alterations during the 12 month storage at 5 °C, which were associated with lycopene stability at 5 °C for 10 months. The nanoemulsion showed partial aggregation in cell culture medium at 37 °C after 24 h. NanoLPG at 0.10 mg/mL exhibited radical scavenging activity equivalent to 0.043 ± 0.002 mg Trolox/mL. The in vivo studies did not reveal any significant changes in clinical, behavioral, hematological, biochemical, and histopathological parameters in mice orally treated with nanoLPG at 10 mg/kg for 28 days. In addition, nanoLPG successfully delivered lycopene to the liver, kidney and prostate in mice, improved its cytotoxicity against DU-145 prostate cancer cells—probably by pathway independent on classical necrosis and apoptosis—and did not affect PBMC viability. Conclusions Thus, nanoLPG stands as a promising and biosafe lycopene delivery system for further development of nanotechnology-based health products. Graphical Abstract

In addition to the morphophysiological changes experienced by amphibians during metamorphosis, they must also deal with a different set of environmental constraints when they shift from the water to the land. We found that Pithecopus azureus secretes a single peptide ([M + H]+ = 658.38 Da) at the developmental stage that precedes the onset of terrestrial behaviour. De novo peptide and cDNA sequencing revealed that the peptide, named PaT-2, is expressed in tandem and is a member of the tryptophyllins family. In silico studies allowed us to identify the position of reactive sites and infer possible antioxidant mechanisms of the compounds. Cell-based assays confirmed the predicted antioxidant activity in mammalian microglia and neuroblast cells. The potential neuroprotective effect of PaT-2 was further corroborated in FRET-based live cell imaging assays, where the peptide prevented lipopolysaccharide-induced ROS production and glutamate release in human microglia. In summary, PaT-2 is the first peptide expressed during the ontogeny of P. azureus , right before the metamorphosing froglet leaves the aquatic environment to occupy terrestrial habitats. The antioxidant activity of PaT-2, predicted by in silico analyses and confirmed by cell-based assays, might be relevant for the protection of the skin of P. azureus adults against increased O 2 levels and UV exposure on land compared with aquatic environments.

Metabolic syndrome, especially its component related to dyslipidemia, is related to the development of nonalcoholic fatty liver disease (NAFLD), which is a disease with a significant global prevalence. Supplementation with omega-3 polyunsaturated fatty acids emerged as a complementary therapeutic possibility for dyslipidemia, but its benefits are questioned. This paper aims at evaluating the effects of fish oil supplementation in rats with hypercholesterolemia induced by hypercholesterolemic diet (HD). The study design is based on an experimental model in which the animals were randomly divided into 3 groups: G1 (standard commercial feed + saline solution); G2 (hypercholesterolemic diet + saline solution) and G3 (hypercholesterolemic diet + fish oil) over a period of 16 weeks. Metabolic control parameters and oxidative stress biomarkers were evaluated according to standardized methodologies. The G3 group showed significantly lower values of plasma concentrations of TG, and hepatic myeloperoxidase as well as higher erythrocyte superoxide dismutase activity (p < 0.05). Regarding histopathological analysis, there was lipid accumulation in the liver of animals from group G2; meanwhile, hepatocytes reorganization and expressive reduction of lipid vacuoles and hepatic TG content was observed in group G3. This study demonstrated how fish oil supplementation reduced the plasma concentration and hepatic content of triglycerides, as well as liver tissue damage in histopathological analysis.