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Talita Katiane Brito, 1, 2,* Rony Lucas Silva Viana, 2, 3,* Cláudia Jassica Gonçalves Moreno, 3, 4 Jefferson da Silva Barbosa, 1, 2, 5 Francimar Lopes de Sousa Júnior, 6 Mayara Jane Campos de Medeiros, 6 Raniere Fagundes Melo-Silveira, 2, 3 Jailma Almeida-Lima, 1–3 Daniel de Lima Pontes, 6 Marcelo Sousa Silva, 3, 4, 7 Hugo Alexandre Oliveira Rocha 1–3 1Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte 59012-570, Brazil; 2Laboratory of Biotechnology of Natural Polymers (BIOPOL), Department of Biochemistry, Center of Biosciences, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte 59078-970, Brazil; 3Postgraduate Program in Biochemistry, Federal University of Rio Grande do Norte UFRN), Natal, Rio Grande do Norte 59078-970, Brazil; 4Laboratory of Immunoparasitology, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte 59012-570, Brazil; 5Federal Institute of Education, Science and Technology of Rio Grande do Norte (IFRN), Natal, Rio Grande do Norte 59500-000, Brazil; 6Laboratory of Chemistry of Coordination and Polymers (LQCPol), Institute of Chemistry, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte 59078-970, Brazil; 7Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, New University of Lisbon, Lisboa 1349-008, Portugal*These authors contributed equally to this workCorrespondence: Hugo Alexandre Oliveira RochaLaboratory of Biotechnology of Natural Polymers (BIOPOL), Department of Biochemistry, Center of Biosciences, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte 59078-970, BrazilEmail hugo@cb.ufrn.brBackground: Chagas disease, also known as American Trypanosomiasis, is caused by the protozoan Trypanosoma cruzi. It is occurring in Americas, including USA and Canada, and Europe and its current treatment involves the use of two drugs as follows: benznidazole (BNZ) and nifurtimox, which present high toxicity and low efficacy during the chronic phase of the disease, thus promoting the search for more effective therapeutic alternatives. Amongst them xylan, a bioactive polysaccharide, extracted from corn cob.Methods: Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy (FITR), Raman spectroscopy, energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy, atomic force microscopy, plasma optical emission spectroscopy (ICP-OES), dynamic light scattering (DLS) have been used to characterize the silver-xylan nanoparticles (NX). Their cytotoxicity was evaluated with 3-bromo(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) test. MTT and flow cytometry were used to ascertain the anti-Trypanosoma cruzi activity.Results: UV-Vis spectroscopy gave plasmon resonance ranging between 400 and 450 nm while FITC and Raman spectroscopy proved nano interface functionalized with xylan. ICP-OES data showed NX with xylan (81%) and silver (19%). EDS showed NX consisting of carbon (59.4%), oxygen (26.2%) and silver (4.8%) main elements. Spherical NX of 55 nm average size has been depicted with SEM and AFM, while DLS showed 102 ± 1.7 nm NX. The NX displayed negligible cytotoxicity (2000 μg/mL). NX (100 μg/mL) was more effective, regardless of experiment time, in affecting the ability of parasites to reduce MTT than BZN (100 μg/mL). In addition, NX (100 μg/mL) induced death of 95% of parasites by necrosis.Conclusion: This is the first time silver nanoparticles are presented as an anti-Trypanosoma cruzi agent and the data point to the potential application of NX to new preclinical studies in vitro and in vivo.Keywords: xylan, silver nanoparticles, Trypanosoma cruzi, benznidazole

A 12.4 kDa laminarin (LM) composed of β(1→3)-glucan with β(1→6)-branches was extracted from brown seaweed Lobophora variegata and modified via carboxylation using dielectric barrier discharge (LMC), conjugation with gallic acid (LMG), and sulfation (LMS). Analyses of the chemical composition of LMC, LMG, and LMS yielded 11.7% carboxyl groups, 1.5% gallic acid, and 1.4% sulfate content, respectively. Antioxidant activities of native and modified laminarins were assessed using six different in vitro methods. Sulfation stopped the antioxidant activities of LM. On the other hand, carboxylation improved cooper chelation (1.2 times). LMG was found to be a more efficient antioxidant agent than LM in terms of copper chelation (1.3 times), reducing power (1.3 times), and total antioxidant capacity (80 times). Gallic acid conjugation was further confirmed using Fourier transform infrared spectroscopy (FT-IR) and one- and two-dimensional NMR spectroscopy analyses. LMG also did not induce cell death or affect the cell cycle of Madin-Darby canine kidney (MDCK) cells. On the contrary, LMG protected MDCK cells from H 2 O 2 -induced oxidative damage. Taken together, these results show that LMG has the potent antioxidant capacity, and, therefore, potential applications in pharmacological and functional food products.

Nitric oxide (NO) and nitroxyl (HNO) have gained broad attention due to their roles in several physiological and pathophysiological processes. Remarkably, these sibling species can exhibit opposing effects including the promotion of angiogenic activity by NO compared to HNO, which blocks neovascularization. While many NO donors have been developed over the years, interest in HNO has led to the recent emergence of new donors. However, in both cases there is an expressive lack of iron-based compounds. Herein, we explored the novel chemical reactivity and stability of the trans-[Fe(cyclam)(NO)Cl]Cl 2 (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex. Interestingly, the half-life (t 1/2 ) for NO release was 1.8 min upon light irradiation, vs 5.4 h upon thermal activation at 37 °C. Importantly, spectroscopic evidence supported the generation of HNO rather than NO induced by glutathione. Moreover, we observed significant inhibition of NO donor- or hypoxia-induced HIF-1α (hypoxia-inducible factor 1α) accumulation in breast cancer cells, as well as reduced vascular tube formation by endothelial cells pretreated with the trans-[Fe(cyclam)(NO)Cl]Cl 2 complex. Together, these studies provide the first example of an iron-nitrosyl complex with anti-angiogenic activity as well as the potential dual activity of this compound as a NO/HNO releasing agent, which warrants further pharmacological investigation., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The treatment of chronic wounds is considered a public health problem. When the condition affects at-risk groups such as those with diabetics, it becomes a great clinical challenge. In this work, we evaluated the healing effects of a new zinc complex, [Zn(phen)(van) 2 ], identified as ZPV, which was synthesized, characterized and associated with chitosan (CS) membranes and tested on cutaneous wounds of diabetic rats. Chitosan membranes were modified by Schiff base reaction with the complex under two experimental conditions (14 and 21 days), resulting in membranes with concentrations of complex equal to 0.736 μmol cm -2 (CS-ZPV1) and 1.22 μmol cm -2 (CS-ZPV2). Release assays in aqueous medium indicated that the membranes release the complex gradually when exposed to an aqueous medium. Diabetes was inducted in Wistar rats using 40 mg/kg (i.v.) streptozotocin. On the 7th day after diabetic induction, a circular excision on the skin (1.0 cm) was performed with a punch. The lesions were treated with the pure chitosan membrane and the membrane associated with the zinc-vanillin complex in two different doses. Skin samples were subjected to macroscopic and histopathological analyses, cytokine (TNF-α, IL-1β, and IL-10) quantification and reverse transcriptase polymerase chain reaction (TGF-β and VEGF) assays. The analyses showed a decrease in wound size, reepithelialization, angiogenic stimulus, collagen deposition, and reduced levels of TNF-α and IL-1β as well as increased IL-10 and gene expression of TGF-β and VEGF. The evaluated parameters suggest that CS-ZPV in the two concentrations tested may be effective in the treatment of chronic wounds.