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ABSTRACT Objective: To assess the effects of cobalt chloride (CoCl2) as a hypoxia mimicking agent on human umbilical cord mesenchymal stem cells (hUCMSCs) expression of HIF-1α and mTOR for use in regenerative dentistry. Material and Methods: Human umbilical cord mesenchymal stem cells were isolated and then cultured. The characteristics of stemness were screened and confirmed by flow cytometry. The experiment was conducted on hypoxia (H) and normoxia (N) groups. Each group was divided and incubated into 24-, 48-, and 72-hours observations. Hypoxic treatment was performed using 100 µM CoCl2 on 5th passage cells in a conventional incubator (37°C; 5CO2). Then, immunofluorescence of HIF-1α and mTOR was done. Data was analyzed statistically using One-way ANOVA and Tukey's HSD. Results: Significant differences were found between normoxic and hypoxic groups on HIF-1α (p=0.015) and mTOR (p=0.000) expressions. The highest HIF-1α expression was found at 48 hours in the hypoxia group, while for mTOR at 24 hours in the hypoxia group. Conclusion: Hypoxia using cobalt chloride was able to increase human umbilical cord mesenchymal stem cells expression of HIF-1α and mTOR.
Assuntos
Humanos , Cordão Umbilical/citologia , Cloretos/química , Cobalto/química , Células-Tronco Mesenquimais/citologia , Hipóxia/patologia , Análise de Variância , Citometria de FluxoRESUMO
Iron is a key element in cell function; however, its excess in iron overload conditions can be harmful through the generation of reactive oxygen species (ROS) and cell oxidative stress. Activity of Na,K-ATPase has been shown to be implicated in cellular iron uptake and iron modulates the Na,K-ATPase function from different tissues. In this study, we determined the effect of iron overload on Na,K-ATPase activity and established the role that isoforms and conformational states of this enzyme has on this effect. Total blood and membrane preparations from erythrocytes (ghost cells), as well as pig kidney and rat brain cortex, and enterocytes cells (Caco-2) were used. In E1-related subconformations, an enzyme activation effect by iron was observed, and in the E2-related subconformations enzyme inhibition was observed. The enzyme's kinetic parameters were significantly changed only in the Na+ curve in ghost cells. In contrast to Na,K-ATPase α2 and α3 isoforms, activation was not observed for the α1 isoform. In Caco-2 cells, which only contain Na,K-ATPase α1 isoform, the FeCl3 increased the intracellular storage of iron, catalase activity, the production of H2O2 and the expression levels of the α1 isoform. In contrast, iron did not affect lipid peroxidation, GSH content, superoxide dismutase and Na,K-ATPase activities. These results suggest that iron itself modulates Na,K-ATPase and that one or more E1-related subconformations seems to be determinant for the sensitivity of iron modulation through a mechanism in which the involvement of the Na, K-ATPase α3 isoform needs to be further investigated.
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Trifosfato de Adenosina/metabolismo , Cloretos/química , Compostos Férricos/química , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Células CACO-2 , Cloretos/metabolismo , Enterócitos/citologia , Enterócitos/metabolismo , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Compostos Férricos/metabolismo , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Cinética , Ratos , ATPase Trocadora de Sódio-Potássio/genética , SuínosRESUMO
Polarizable force fields are gradually becoming a common choice for ionic soft matter, in particular, for molecular dynamics (MD) simulations of ionic liquids (ILs) and deep eutectic solvents (DESs). The CL&Pol force field introduced in 2019 is the first general, transferable, and polarizable force field for MD simulations of different types of DESs. The original formulation contains, however, some problems that appear in simulations of ethaline and may also have a broader impact. First, the originally proposed atomic diameter parameters are unbalanced, resulting in too weak interactions between the chlorides and the hydroxyl groups of the ethylene glycol molecules. This, in turn, causes an artificial phase separation in long simulations. Second, there is an overpolarization of chlorides due to strong induced dipoles that give rise to the presence of peaks and antipeaks at very low q-vector values (2.4 nm-1) in the partial components of the structure factors. In physical terms, this is equivalent to overestimated spatial nanoscale heterogeneity. To correct these problems, we adjusted the chloride-hydroxyl radial distribution functions against ab initio data and then extended the use of the Tang-Toennis damping function for the chlorides' induced dipoles. These adjustments correct the problems without losing the robustness of the CL&Pol force field. The results were also compared with the nonpolarizable version, the CL&P force field. We expect that the corrections will facilitate reliable use of the CL&Pol force field for other types of DESs.
Assuntos
Cloretos , Líquidos Iônicos , Cloretos/química , Solventes Eutéticos Profundos , Líquidos Iônicos/química , Simulação de Dinâmica Molecular , Solventes/químicaRESUMO
Two square-planar coordination compounds, namely [Cu(CPYA)Cl2] (1) and [Pd(CPYA)Cl2] (2), were prepared from the ligand 4-chloro-N-(pyridin-2-ylmethyl)aniline (CPYA) and two chloride salts, and were fully characterized, including by X-ray diffraction. Spectroscopic, electrophoretic and AFM studies revealed that the two isostructural compounds were interacting differently with DNA. In both cases, the initial interaction involves electrostatic contacts of the CPYA ligand in the minor groove (as suggested by molecular docking), but subsequent strong binding occurs with the palladium(II) complex 2, whereas the binding with the copper complex 1 is weaker and concentration dependent. The strong binding of 2 eventually leads to the cleavage of the double strand and the redox activity of 1 allows to oxidatively cleave the biomolecule.
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Cloretos/química , Cobre/química , DNA/química , Paládio/química , Dicroísmo Circular , Cristalografia por Raios X , Corantes Fluorescentes , Ligação de Hidrogênio , Modelos Moleculares , Estrutura MolecularRESUMO
Cellulose nanofibers (CNF) are renewable and biodegradable nanomaterials with attractive barrier, mechanical and surface properties. In this work, three different recombinant enzymes: an endoglucanase, a xylanase and a lytic polysaccharide monooxygenase, were combined to enhance cellulose fibrillation and to produce CNF from sugarcane bagasse (SCB). Prior to the enzymatic catalysis, SCB was chemically pretreated by sodium chlorite and KOH, while defibrillation was accomplished via sonication. We obtained much longer (µm scale length) and more thermostable (resisting up to 260 °C) CNFs as compared to the CNFs prepared by TEMPO-mediated oxidation. Our results showed that a cooperative action of the set of hydrolytic and oxidative enzymes can be used as a "green" treatment prior to the sonication step to produce nanofibrillated cellulose with advanced properties.
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Celulase/química , Celulose/química , Endo-1,4-beta-Xilanases/química , Oxigenases de Função Mista/química , Nanofibras/química , Biocatálise , Biodegradação Ambiental , Cloretos/química , Óxidos N-Cíclicos/química , Química Verde , Humanos , Hidrólise , Hidróxidos/química , Nanofibras/ultraestrutura , Oxirredução , Polissacarídeos/química , Compostos de Potássio/química , Saccharum/química , SonicaçãoRESUMO
Safety on the use of magnetic nanomaterials (MNMs) has become an active topic of research given all the recent applications of these materials in various fields. It is known that the toxicity of MNMs depends on size, shape, and surface functionalization. In this study, we evaluate the biocompatibility with different aquatic organisms of engineered MNMs-CIT with excellent aqueous dispersion and long-term colloidal stability. Primary producers (the alga Pseudokirchneriella subcapitata), primary consumers (the rotifer Lecane papuana), and predators (the fish, Danio rerio) interacted with these materials in acute and sub-chronic toxicity tests. Our results indicate that P. subcaptita was the most sensitive taxon to MNMs-CIT. Inhibition of their population growth (IC50 = 22.84 mg L-1) elicited cell malformations and increased the content of photosynthetic pigments, likely due to inhibition of cell division (as demonstrated in AFM analysis). For L. papuana, the acute exposure to MNMs shows no significant mortality. However, adverse effects such as decreased rate of population and altered swimming patterns arise after chronic interaction with MNMs. For D. rerio organisms on early life stages, their exposure to MNMs results in delayed hatching of eggs, diminished survival of larvae, altered energy resources allocation (measured as the content of total carbohydrates, lipids, and protein), and increased glucose demand. As to our knowledge, this is the first study that includes three different trophic levels to assess the effect of MNMs in aquatic organisms; furthermore, we demonstrated that these MNMs pose hazards on aquatic food webs at low concentrations (few mgL-1).
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Organismos Aquáticos/efeitos dos fármacos , Cloretos/toxicidade , Compostos Férricos/toxicidade , Compostos Ferrosos/toxicidade , Nanoestruturas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/análise , Cloretos/química , Compostos Férricos/química , Compostos Ferrosos/química , Cadeia Alimentar , Larva/efeitos dos fármacos , Fenômenos Magnéticos , Microalgas/efeitos dos fármacos , Nanoestruturas/química , Tamanho da Partícula , Rotíferos/efeitos dos fármacos , Propriedades de Superfície , Poluentes Químicos da Água/química , Peixe-Zebra/crescimento & desenvolvimentoRESUMO
Neglected tropical diseases (NTDs) are responsible for over 500,000 deaths annually and are characterized by multiple disabilities. Leishmaniasis and Chagas diseases are among the most severe NTDs, and are caused by the Leishmania sp and Trypanosoma cruzi, respectively. Glucantime, pentamidine, and miltefosine are commonly used to treat leishmaniasis, whereas nifurtimox, benznidazole are current treatments for Chagas disease. However, these treatments are associated with drug resistance and severe side effects. Hence, the development of synthetic products, especially those containing N02, F, or Cl, are known to improve biological activity. The present work summarizes the information on the antileishmanial and antitrypanosomal activity of nitro-, chloro-, and fluorosynthetic derivatives. Scientific publications referring to halogenated derivatives in relation to antileishmanial and antitrypanosomal activities were hand-searched in databases such as SciFinder, Wiley, Science Direct, PubMed, ACS, Springer, Scielo, and so on. According to the literature information, more than 90 compounds were predicted as lead molecules with reference to their IC50/EC50 values in in vitro studies. It is worth mentioning that only active compounds with known cytotoxic effects against mammalian cells were considered in the present study. The observed activity was attributed to the presence of nitro-, fluoro-, and chloro-groups in the compound backbone. All in all, nitro and halogenated derivatives are active antileishmanial and antitrypanosomal compounds and can serve as the baseline for the development of new drugs against leishmaniasis and Chagas disease. However, efforts in in vitro and in vivo toxicity studies of the active synthetic compounds is still needed. Pharmacokinetic studies and the mechanism of action of the promising compounds need to be explored. The use of new catalysts and chemical transformation can afford unexplored halogenated compounds with improved antileishmanial and antitrypanosomal activity.
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Antiprotozoários , Doença de Chagas , Cloretos/química , Fluoretos/química , Leishmaniose , Dióxido de Nitrogênio/química , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Doença de Chagas/tratamento farmacológico , Desenho de Fármacos , Humanos , Leishmaniose/tratamento farmacológico , Trypanosoma cruziRESUMO
PURPOSE: To develop a new wound dressing composed of alginate and Aloe vera gel and cross-linked with zinc ions. METHODS: The aloe-alginate film was characterized using scanning electron microscopy (SEM), swelling profile, mechanical properties, polysaccharide content and X-ray diffraction (XRD). Thirty Wistar rats were divided in two groups a) treated with aloe-alginate film and b) control (treated with sterile gauze). Wound contraction measurements and hystological analysis were performed on 7th, 14th and 21st days after wound surgery. RESULTS: The aloe-alginate film presented adequated mechanical resistance and malleability for application as wound dressing. There was no statistical difference in wound contraction between two groups. Histological assay demonstrated that aloe-alginate film presented anti-inflammatory activity, stimulated angiogenesis on proliferative phase and a more significant increased in collagen type I fibers and decreased type III fibers which promoted a mature scar formation when compared to control. CONCLUSIONS: The aloe-alginate film showed adequate physicochemical characteristics for wound dressing applications. The in vivo assay demonstrated that aloe-alginate film enhanced the healing process of incisional skin wounds.
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Alginatos , Aloe , Cloretos , Preparações de Plantas , Cicatrização , Compostos de Zinco , Alginatos/farmacologia , Animais , Cloretos/química , Cloretos/farmacologia , Preparações de Plantas/farmacologia , Ratos , Ratos Wistar , Cicatrização/efeitos dos fármacos , Compostos de Zinco/química , Compostos de Zinco/farmacologiaRESUMO
The environmental impacts related to Portland cement production in terms of energy consumption, the massive use of natural resources and CO2 emissions have led to the search for alternative cementitious materials. Among these materials, alkali-activated cements based on fly ash (FA) have been considered for concrete production with greater sustainability. In the present article, the chemical durability properties (resistance to sulphates, chloride permeability, and resistance to carbonation) of a hybrid alkali-activated concrete based on fly ash-ordinary Portland cement (FA/OPC) with proportions of 80%/20% were evaluated. It is noted that the FA was a low-quality pozzolan with a high unburned carbon content (20.67%). The results indicated that FA/OPC concrete had good durability with respect to the OPC concrete, with 95% less expansion in the presence of sodium sulphate and a 2% strength loss at 1100 days, compared with the 56% strength loss of the OPC concrete. In addition, FA/OPC showed lower chloride permeability. On the contrary, the FA/OPC was more susceptible to carbonation. However, the residual compressive strength was 23 MPa at 360 days of CO2 exposure. Based on the results, FA/OPC, using this type of FA, can be used as a replacement for OPC in the presence of these aggressive agents in the service environment.
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Álcalis/química , Carbono/química , Cloretos/química , Cinza de Carvão/química , Materiais de Construção/análise , Sulfatos/químicaRESUMO
Meat emulsions were made with 50% of phosphate level commonly used in the meat industry, and 0, 25, and 50% NaCl reduction. In addition, salt replacers (KCl, CaCl2, or MgCl2) were used in the formulations with 25 and 50% salt reduction, corresponding to 10 and 20% of the total amount of salts added, respectively. After embedding in casings, the samples were sonicated (25 kHz and 230 W) in an ultrasonic bath (US) at 20 °C for 0, 18, and 27 min. The addition of CaCl2 or MgCl2 impaired (P < .05) the technological properties of the low-sodium samples. Defects caused by NaCl reduction were not eliminated by 18-min US. However, the combination of KCl and 27-min US eliminated the technological defects caused by the 50% NaCl reduction, with no major impact on lipid oxidation during storage (21 days/4 °C), as observed in the TBARS and sensory profile results. Therefore, it is possible to produce low-phosphate and low-sodium meat emulsions.