Atividade de modelos biomiméticos de fosfatases ácidas púrpuras sobre ácidos nucleicos

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-graduação em QuímicaComplexos biomiméticos do sítio ativo das PAPs foram sintetizados com o objetivo de elucidar o papel das PAPs nos sistemas vivos e simultaneamente encontrar novas aplicações para estes complexos como nucleases sintéticas. Com este intuito, foi testada a atividade de uma série de complexos heterodinucleares Fe3+M2+, usando o ligante assimétrico H2BPBPMP. Os complexos são: FeCuOAc, FeCuOH, FeZnOAc, FeZnOH, FeMnOH e FeNiOAc. O DNA plasmidial foi utilizado como modelo para testar a clivagem da ligação fosfato pelos complexos. Foram testadas diferentes condições de pH e concentração dos complexos. As reações também foram realizadas na presença de captadores de radicais livres e na ausência de oxigênio. Para verificar a interação complexo/DNA foram realizados experimentos com Distamicina e titulação espectrofotométrica UV-Vis. Todos os complexos, exceto FeNiOAc, foram capazes de clivar DNA por um mecanismo hidrolítico em baixas concentrações do complexo (2,5 µM) a 37 oC em pH próximo ao fisiológico (faixa de 6,0 a 7,0). O complexo FeNiOAc não cliva o DNA, mas pode se ligar ao DNA e alterar significativamente sua mobilidade. O complexo FeCuOAc é o mais ativo da série apresentando uma aceleração de 2,71 x 107 vezes quando comparado com o valor do DNA não catalisado, seguido por, FeMnOH, FeZnOAc, FeCuOH e FeZnOH

Development and characterization of biointeractive gelatin wound dressing based on extract of Punica granatum Linn

Punica granatum Linn (pomegranate) extracts have been proposed for wound healing due to their antimicrobial, antioxidant, and anti-inflammatory properties. In this work, we designed biointeractive membranes that contain standard extracts of P. granatum for the purpose of wound healing. The used standard extract contained 32.24 mg/g of gallic acid and 41.67 mg/g of ellagic acid, and it showed high antioxidant activity (the concentration of the extract that produces 50% scavenging (IC50) 1.715 µg/mL). Compared to the gelatin-based membranes (GEL), membranes containing P. granatum extracts (GELPG) presented a higher maximal tension (p=0.021) and swelling index (p=0.033) and lower water vapor permeability (p=0.003). However, no difference was observed in the elongation and elastic modulus of the two types of membranes (p > 0.05). Our wound-healing assay showed that a GELPG-treated group experienced a significant increase compared to that of the control group in their wound contraction rates on days 3 (p < 0.01), 7 (p < 0.001), and on day 14 (p < 0.001). The GELPG membranes promoted major histological changes in the dynamics of wound healing, such as improvements in the formation of granular tissue, better collagen deposition and arrangement, and earlier development of cutaneous appendages. Our results suggest that a biointeractive gelatin-based membrane containing P. granatum extracts has a promising potential application for dressings that are used to treat wounds.The research was funded by FAPITEC/SE (Fundação de Apoio à Pesquisa e Inovação Tecnológica do Estado de Sergipe) and by the Brazilian Bureau of Research. T. Pashirova received the financial support from the government assignment for the FRC Kazan Scientific Center of Russian Academy of Sciences. E.B. Souto received the support from the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020, granted by the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds and co-financed by FEDER under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Epidemiology of COVID-19 in the State of Sergipe/Brazil and Its Relationship with Social Indicators

A pandemic is capable of generating a great impact, not only from the point of view of health, but also socioeconomically. In March 2020, the World Health Organization (WHO) declared that a new pandemic situation had arisen, due to the SARS-CoV-2 virus, whose probable origin was zoonotic. The largest number of cases of this disease is concentrated in the United States of America (USA), India, and Brazil. The mortality rate is estimated at 3.4%, but regional differences may exist, and places with a high demographic density have become true epicentres and may be related to higher rates of transmission. In addition to the above, lower human development indexes (HDI) can be related to worse outcomes, especially in the North and Northeast regions of Brazil since they are the least developed places. The Northeast region is the second-most-affected place in the number of COVID-19 cases in Brazil. An analytical observational study of an ecological type was carried out from April to October 2020 to assess the epidemiological situation of COVID-19 in the state of Sergipe and specifically to analyse the incidence of cases and deaths resulting from COVID-19 in the different health regions of the state of Sergipe, in relation to the values of the HDI and demographic density. During the study period, 84,325 cases of COVID-19 were identified, in which 2205 resulted in death. In most of the regions studied, there was a positive association between the number of cases and deaths and the greater the demographic density, but there was no increase in the risk of becoming ill, nor of dying the lower the HDI. Large and crowded cities are places of greatest vulnerability to illness, due to their greater capacity of transmitting the virus; however, further studies are needed to identify other factors that are decisive in the outcomes of this new disease.This research received no external funding.info:eu-repo/semantics/publishedVersio

Development of a manometric monitoring method for early detection of air microbiological contamination in the bloodstream

Atmospheric air is a microbial habitat of pathogenic bioaerosols that may pose serious risks to humans. A commonly laboratory-based approach for the diagnosis of such infections in the bloodstream is the blood culture analysis. Its clinical relevance is attributed to the fact that these infections are characterized by high rates of morbidity and mortality, requiring the need for efficient methods for rapid diagnosis. For this reason, our study aimed to develop a method of manometric monitoring for the rapid detection of viable microorganisms in blood culture vials. A methodology was developed to detect pressure variation in intra-vials through a manometric instrument that was coupled to vials of blood culture containing culture broth that allowed microbial growth. This device allowed the early detection of microbial activity based on the production or use of intra-flask gases as a result of microbial metabolic activity. The analyzed variables were the pressure as a function of time, microbial species, and culture medium. The highest pressure found in the flasks without microorganisms was 40 mmHg between 2 and 6 h, and the lowest pressure was 42 mmHg between 21 and 24 h. The variation of the internal pressure in blood culture flasks according to different groups of microorganisms as a function of time demonstrated that the fermentative gram-negative bacilli and gram-positive cocci exhibited a significant increase in relation to their respective control groups (p < 0.001). The non-fermenting gram-negative bacilli showed expected results in relation to the pressure variation in which the production of negative pressures was noticed during the period of analysis, with a significant difference with respect to their control groups (p < 0.001). The developed methodology for the early detection of microorganisms responsible for bloodstream infection was demonstrated to be effective.e Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe-Program Centelha (FAPITEC/SE) and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Portuguese Science and Technology Foundation (FCT) through the project UIDB/04469/2020 (strategic fund) funded by national funds, and co-financed Education (FCT/MEC) from national funds and FEDER, under the Partnership Agreement PT2020info:eu-repo/semantics/publishedVersio

Development and evaluation of superabsorbent hydrogels based on natural polymers

Superabsorbent hydrogels (SAHs) are three dimensional networks formed by polymers that can absorb aqueous solution of over 100% of their initial weight. This work aimed to develop and characterize SAHs of Chitosan/Xanthan gum (CG), Chitosan/Alginate (CA) and controlled Chitosan (C), Xanthan gum (G), and Alginate (A) produced using “onion-like” methodology. The swelling performance, the morphological structure, the crystallinity, and the Fourier transformed infrared spectroscopy characteristics of SAH were used for the characterization of polyelectrolytes complex. Swelling analysis showed that chitosan has a strong influence on the maintenance of hydrogels structure after swelling, mainly in the acid environment (pH=2). The chitosan hydrogel presented around 3000% of acidic fluid absorption after 24 h. The chitosan:xanthan gum (1:1 and 2:1 named as C1G1 and C2G1, respectively) hydrogels were the best combination regarding swelling performance in an acid environment, reaching 1665% and 2024%, respectively, as well at pH 7.0, presenting 1005% (C1G1) and 667% (C2G1). Scanning electron microscopy analysis showed samples with pores, and with different shapes. The X-ray diffraction showed the presence of a characteristic peak at 2θ=20° in all developed composition because of the crystalline nature of chitosan. This work shows the possibility of developing eco-friendly biopolymer-based SAHs at a low cost with a good swelling capacity and stability.The research was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES/Brazil), Fundação de Amparo a Pesquisa do Estado de Sergipe (FAPITEC, MS/CNPq/FAPITEC/SE/SESN◦06/2018) e do Conselho Nacional de Pesquisas (CNPq, Apoio a Projetos de Pesquisa/MCTI/CNPQ/Universal 14/2014) for supporting funds. EBS acknowledges the Portuguese Science and Technology Foundation (FCT) for the funded projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund) financed from national funds, and cofinanced education (FCT/MEC) from national funds and FEDER, under the Partnership Agreement PT2020. J.J. acknowledges the Ministry of Science and Technical Development of the Republic of Serbia, through Contract Number 200051 172015 OI.info:eu-repo/semantics/publishedVersio

Effectiveness of different cellulose-based filtration materials against inhalation of SARS-CoV-2-like particles

The respiratory protection equipment (RPE) used by health professionals consists of an essential device to prevent infectious diseases, especially those caused by biological agents such as the coronavirus (SARS-CoV-2). The current epidemiological panorama is worrying, and the context of creation and production of the mask has emerged as an alternative to RPE to face the public health crisis worldwide. The aim of this work is to present a low-cost alternative as an FFP2-like filter for a reusable respirator face mask. This study presents the comparison of different cellulose-based filtering materials performed by retention testing, time saturation testing, aerosol penetration testing, nanoparticle (~140 nm) filtration testing, bacterial filtration efficiency (BFE), analysis of material morphology and usability. The reusable respirator face mask used in this study is an open-source innovation, using 3D printing. Cotton disc proved to be the best filter material for the reusable mask, with satisfactory results and a performance similar to that shown by the N95-type mask. The cotton disc ensured effectiveness over 6 h of use, and after that, the reusable respirator face mask (here, Delfi-TRON®) needed to be sanitized and replenished with a new cotton disc. Upon preliminary analyses of filtration efficiency, the selected filter was shown to be a low-cost biodegradable and biocompatible alternative.info:eu-repo/semantics/publishedVersio

Histological evidence of wound healing improvement in rats treated with oral administration of hydroalcoholic extract of Vitis labrusca

Plant extracts rich in phenolic compounds have been demonstrated to accelerate wound healing, but their use by oral route has been poorly studied. The leaves of Vitis labrusca are rich in phenolic acids and flavonoids. The goal of this study was to assess the healing properties of the oral administration of hydroalcoholic extract of V. labrusca leaves (HEVL) in a murine model. HEVL was obtained by Soxhlet and dynamic maceration, and their yield and phenolic acids and flavonoid contents were determined. For the wound healing assay, 8 mm wounds were performed on the back of 48 Wistar rats, assigned into four groups (n=12): CTR (distilled water), HEVL100, HEVL200, and HEVL300 (HEVL at 100, 200, and 300 mg/kg, respectively). On days 7 and 14, wound closure rates were assessed, and the healing wounds were subjected to histological analysis. Soxhlet-obtained extract was selected for the wound healing assay because it provided a higher yield and phenolic acid and flavonoid contents. HEVL significantly reduced leukocytosis in the peripheral blood (p < 0.05), accelerated wound closure (p < 0.05), and improved collagenization (p < 0.05) on day 7, as well as enhanced the epidermal tissue thickness (p < 0.001) and elastic fiber deposition on day 14 (p < 0.01). Furthermore, HEVL promoted an increase in the histological grading of wound healing on both days 7 and 14 (p < 0.01). The doses of 200 and 300 mg/kg provided better results than 100 mg/Kg. Our data provide histological evidence that the oral administration of HEVL improves wound healing in rodents. Therefore, the extract can be a potential oral medicine for healing purposes.Brazilian Council for Research Support (CNPq) and the Foundation of research and technological innovation of Sergipe/Brazil (FAPITEC), and by the Portuguese Science and Technology Foundation (FCT/MCT), European Funds (PRODER/COMPETE)– project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020info:eu-repo/semantics/publishedVersio

Cymbopogon winterianus essential oil attenuates bleomycin-induced pulmonary fibrosis in a murine model

The essential oil of Cymbopogon winterianus (EOCW) is a natural product with antioxidant, anti-inflammatory, and antifibrotic properties. We studied the effect of EOCW in the progression of histological changes of pulmonary fibrosis (PF) in a rodent model. The oil was obtained by hydrodistillation and characterized using gas chromatographymass spectrometry. Intratracheal instillation of bleomycin was performed in 30 rats to induce PF, while Sham animals were subjected to instillation of saline solution. The treatment was performed using daily oral administration of distilled water, EOCW at 50, 100, and 200 mg/kg, and deflazacort (DFC). After 28 days, hemogram and bronchoalveolar lavage fluid (BALF), tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were assayed. Histological grading of PF, immunohistochemical expression of -smooth muscle actin (-SMA), and transforming growth factor- (TGF-) were also analyzed. The EOCW major compounds were found to be citronellal, geraniol, and citronellol. EOCW significantly reduced inflammation in BALF, reduced MDA levels, and increased SOD activity. EOCW attenuated histological grading of PF and reduced immunohistochemical expression of -SMA and TGF- in a dose-dependent way, likely due to the reduction of oxidative stress, inflammation, and TGF--induced myofibroblast differentiation.This research was financed by the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). EBS wishes to acknowledge the sponsorship of the project UIDB/04469/2020 (strategic fund) from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and was co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Red propolis and its dyslipidemic regulator formononetin: evaluation of antioxidant activity and gastroprotective effects in rat model of gastric ulcer

Propolis has various pharmacological properties of clinical interest, and is also considered a functional food. In particular, hydroalcoholic extracts of red propolis (HERP), together with its isoflavonoid formononetin, have recognized antioxidant and anti-inflammatory properties, with known added value against dyslipidemia. In this study, we report the gastroprotective effects of HERP (50–500 mg/kg, p.o.) and formononetin (10 mg/kg, p.o.) in ethanol and non-steroidal anti-inflammatory drug-induced models of rat ulcer. The volume, pH, and total acidity were the evaluated gastric secretion parameters using the pylorus ligature model, together with the assessment of gastric mucus contents. The anti-Helicobacter pylori activities of HERP were evaluated using the agar-well diffusion method. In our experiments, HERP (250 and 500 mg/kg) and formononetin (10 mg/kg) reduced (p < 0.001) total lesion areas in the ethanol-induced rat ulcer model, and reduced (p < 0.05) ulcer indices in the indomethacin-induced rat ulcer model. Administration of HERP and formononetin to pylorus ligature models significantly decreased (p < 0.01) gastric secretion volumes and increased (p < 0.05) mucus production. We have also shown the antioxidant and anti-Helicobacter pylori activities of HERP. The obtained results indicate that HERP and formononetin are gastroprotective in acute ulcer models, suggesting a prominent role of formononetin in the effects of HERP.This work has been funded by the Fundação de ApoioàPesquisa eàInovação Tecnológica do Estadode Sergipe (FAPITEC/SE), by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).R.L.C.d.A.-J., S.M.T., and J.C.C. received CNPq productivity grants. E.B.S. acknowledges the sponsorship of theproject UIDB/04469/2020 (strategic fund), from the Portuguese Science and Technology Foundation, Ministry ofScience and Education (FCT/MEC) through national funds, and was co-financed by FEDER, under the PartnershipAgreement PT2020. E.N. and A.S. acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D1800014000info:eu-repo/semantics/publishedVersio

A New Heterobinuclear FeIIICuII Complex with a Single Terminal FeIII–O(phenolate) Bond. Relevance to Purple Acid Phosphatases and Nucleases

A novel heterobinuclear mixed valence complex [Fe^IIICu^II(BPBPMP)(OAc)_2]ClO_4, 1, with the unsymmetrical N_5O_2 donor ligand 2-bis[{(2-pyridylmethyl)aminomethyl}-6-{(2-hydroxybenzyl)(2-pyridylmethyl)} aminomethyl]-4-methylphenol (H_2BPBPMP) has been synthesized and characterized. A combination of data from mass spectrometry, potentiometric titrations, X-ray absorption and electron paramagnetic resonance spectroscopy, as well as kinetics measurements indicates that in ethanol/water solutions an [Fe^III-(nu)OH-Cu^IIOH_2]+ species is generated which is the likely catalyst for 2,4-bis(dinitrophenyl)phosphate and DNA hydrolysis. Insofar as the data are consistent with the presence of an Fe_III-bound hydroxide acting as a nucleophile during catalysis, 1 presents a suitable mimic for the hydrolytic enzyme purple acid phosphatase. Notably, 1 is significantly more reactive than its isostructural homologues with different metal composition (Fe^IIIM^II, where M^II is Zn^II, Mn^II, Ni^II,or Fe^II). Of particular interest is the observation that cleavage of double-stranded plasmid DNA occurs even at very low concentrations of 1 (2.5 nuM), under physiological conditions (optimum pH of 7.0), with a rate enhancement of 2.7 x 10^7 over the uncatalyzed reaction. Thus, 1 is one of the most effective model complexes to date, mimicking the function of nucleases