Doxorubicin delivery performance of superparamagnetic carbon multi-core shell nanoparticles: pH dependence, stability and kinetic insight.

In the past decade, magnetic nanoparticles (MNPs) have been among the most attractive nanomaterials used in different fields, such as environmental and biomedical applications. The possibility of designing nanoparticles with different functionalities allows for advancing the biomedical applications of these materials. Additionally, the magnetic characteristics of the nanoparticles enable the use of magnetic fields to drive the nanoparticles to the desired sites of delivery. In this context, the development of new MNPs in new approaches for drug delivery systems (DDSs) for cancer treatment has increased. However, the synthesis of nanoparticles with high colloidal stability triggered drug delivery, and good biocompatibility remains a challenge. Herein, multi-core shell MNPs functionalized with Pluronic ® F-127 were prepared and thoroughly characterized as drug carriers for doxorubicin delivery. The functionalized nanoparticles have an average size of 17.71 ± 4.2 nm, high water colloidal stability, and superparamagnetic behavior. In addition, the nanoparticles were able to load 936 µg of DOX per mg of functionalized nanomaterial. Drug release studies at different pH values evidenced a pH-triggered DOX release effect. An increase of 62% in cumulative drug release was observed at pH simulating tumor endosome/lysosome microenvironments (pH 4.5) compared to physiological conditions (pH 7.4). In addition, an innovative dynamic drug delivery study was performed as a function of pH. The results from this test confirmed the pH-induced doxorubicin release capability of carbon multi-core shell MNPs. The validity of traditional kinetic models to fit dynamic pH-dependent drug release was also studied for predictive purposes.

Synthesis of low-density polyethylene derived carbon nanotubes for activation of persulfate and degradation of water organic micropollutants in continuous mode.

Plastic derived carbon nanotubes (CNTs) were tested as catalysts in persulfate activation for the first time. Four catalysts were prepared by wetness impregnation and co-precipitation (using Al2O3, Ni, Fe and/or Al) and implemented to grow CNTs by chemical vapour deposition (CVD) using low-density polyethylene (LDPE) as carbon feedstock. A catalyst screening was performed in batch mode and the best performing CNTs (CNT@Ni+Fe/Al2O3-cp) led to a high venlafaxine mass removal rate (3.17 mg g-1 h-1) in ultrapure water after 90 min (even with a mixture of micropollutants). Its degradation increased when the matrix was replaced by drinking water and negligibly affected in surface water. A composite polymeric membrane was then fabricated with CNT@Ni+Fe/Al2O3-cp and polyvinylidene fluoride (PVDF), a high venlafaxine mass removal rate in surface water being also observed in 24 h of continuous operation. Therefore, the results herein reported open a window of opportunity for the valorisation of plastic wastes in this catalytic application performed in continuous mode.

The enzyme interactome concept in filamentous fungi linked to biomass valorization.

Biomass represents an abundant and inexpensive source of sugars and aromatic compounds that can be used as raw materials for conversion into value-added bioproducts. Filamentous fungi are sources of plant cell wall degrading enzymes in nature. Understanding the interactions between enzymes is crucial for optimizing biomass degradation processes. Herein, the concept of the interactome is presented as a holistic approach that depicts the interactions among enzymes, substrates, metabolites, and inhibitors. The interactome encompasses several stages of biomass degradation, starting with the sensing of the substrate and the subsequent synthesis of hydrolytic and oxidative enzymes (fungus-substrate interaction). Enzyme-enzyme interactions are exemplified in the complex processes of lignocellulosic biomass degradation. The enzyme-substrate-metabolite-inhibitor interaction also provides a better understanding of biomass conversion, allowing bioproduct production from recalcitrant agro-industrial residues, thus bringing greater value to residual biomass. Finally, technological applications are presented for optimizing the interactome at various levels.

The association between cardiovascular risk factors and major cardiovascular diseases decreases with increasing frailty levels in geriatric outpatients.

BACKGROUND: Frailty marks a process of increasing dysregulation of physiological systems which increases the risk of adverse health outcomes. This study examines the hypothesis that the association between multiple cardiovascular risk factors (CVRF) and cardiovascular diseases (CVD) becomes stronger with increasing frailty severity. METHODS: Cross-sectional analysis of 339 older adults (55.2% women; aged 75.2 ±â€¯9.1 years) from an outpatient geriatric clinic from a middle-income country. The frailty index (FI) was calculated as the proportion of 30 possible health deficits. We assessed hypertension, diabetes, obesity, dyslipidemia, sedentarism and smoking as CVRF (determinants) and myocardial infarction, stroke, heart failure as CVD. Poisson regression models adjusted for age, sex, and education was applied to estimate the association between frailty as well as CVRF (independent variables) with CVD (dependent variable). RESULTS: Of the 339 patients, 18,3% were frail (FI ≥ 0.25) and 32.7% had at least one CVD. Both frailty and CVRF were significantly associated with CVD (PR = 1.03, 95% CI 1.01 to 1.05; p = 0.001, and PR = 1.46, 95% 1.24 to 1.71; p < 0.001, respectively) adjusted for covariates. The strength of the association between CVRF and CVD decreased with increasing frailty levels, as indicated by a significant interaction term of frailty and CVRF (p < 0.001). CONCLUSION: Frailty and CVRF are both associated with CVD, but the impact of CVRF decreases in the presence of frailty. When confirmed in longitudinal studies, randomized controlled trials or causal inference methods like Mendelian randomization should be applied to assess whether a shift from traditional CVRF to frailty would improve cardiovascular outcome in the oldest old.

Opuntia ficus-indica is an excellent eco-friendly biosorbent for the removal of chromium in leather industry effluents.

In Brazil, the leather industry is an important economic segment moving around U$ 3 billions of dollars a year. However, high amounts of water are requested to transform skin animals into leather, causing high wastewater amounts to be consequently produced. A major problem is attached to the presence of chromium in the wastewater from the tanning process. Chromium is a heavy metal potentially toxic both to the environment and to the human health. In order to control the levels of chrome dumped into the environment, Brazilian agencies require the treatment of effluents by the generating source. Thus, this study aimed to develop an alternative method to the removal of chromium in wastewater from the leather industry using the Opuntia ficus-indica biomass as eco-friendly biosorbent. Crude waste samples were collected in a tannery stabilization pond for chromium quantification and further treatments. The powdered Opuntia ficus-indica was obtained from species collected in Pernambuco, Brazil, and its physical parameters and pHPCZ were characterized. Adsorptions studies and acute toxicity were also carried out. The biomass remaining after the sorption was analyzed through scanning electron microscopy and Fourier-transform infrared spectroscopy. The chromium content was above the limit allowed by the Brazilian regulatory agency. In sorption studies, biomass was able to remove 74.8% and 84.88% of Cr (III) using 2.0 g and 4.0 g of biomass, respectively. The surface of biomass is very favorable to biosorption and the chemical bindings among oxygen atoms present in the chemical components of this biomass and the heavy metal was confirmed through infrared spectrum. This study proved that Opuntia ficus-indica is effectively biosorbent to chromium, promising and with low costs for the leather industry, able to reduce its ecotoxicity as proven by chemical and biological assays.

Adsorption of Sudan-IV contained in oily wastewater on lipophilic activated carbons: kinetic and isotherm modelling.

Up to nine kinetic and fourteen isotherm adsorption models are employed to model the adsorption of Sudan IV, a lipophilic model pollutant present in a biphasic mixture of cyclohexane-water system to simulate oily wastewater. Six different modified activated carbons were used as adsorbents. The highest amount adsorbed of Sudan IV was found in the material prepared by successive treatments of the parent commercial activated carbon Norit ROX 0.8 with nitric acid and urea, followed by thermal treatment at 800 °C under continuous flow of nitrogen. Kinetic and isotherm adsorption models can be employed to simulate the process, since the effect of the presence of water in the adsorption of Sudan IV from the cyclohexane phase was found to be negligible, owing to the high lipophilic character of both adsorbent and adsorbate. All kinetic and isotherm coefficients, coupling with statistical parameters (r2, adjusted r2 and sum of squared errors), are determined by non-linear regression fitting and compared to literature data. The model of Avrami is found to be the most appropriate model to represent the adsorption of the pollutant in any of the six modified carbons tested, the highest value of the kinetic constant being 0.055 min-1. The isotherm adsorption is well-modelled by using the general isotherm equation of Tóth and the multilayer Jovanovic expression for the adsorption of Sudan-IV on that material, resulting in a high monolayer uptake capacity (qm = 193.6 mg g-1).

Degradation of methylparaben by sonocatalysis using a Co-Fe magnetic carbon xerogel.

The degradation of methylparaben (MP) through 20 kHz ultrasound coupled with a bimetallic Co-Fe carbon xerogel (CX/CoFe) was investigated in this work. Experiments were performed at actual power densities of 25 and 52 W/L, catalyst loadings of 12.5 and 25 mg/L, MP concentrations between 1 and 4.2 mg/L and initial pH values between 3 and 10 in ultrapure water (UPW). Matrix effects were studied in bottled water (BW) and secondary treated wastewater (WW), as well as in UPW spiked with bicarbonate, chloride or humic acid. The pseudo-first order kinetics of MP degradation increase with power and catalyst loading and decrease with MP concentration and matrix complexity; moreover, the reaction is also favored at near-neutral conditions and in the presence of dissolved oxygen. The contribution of the catalyst is synergistic to the sonochemical degradation of MP and the extent of synergy is quantified to be >45%. This effect was ascribed to the ability of CX/CoFe to catalyze the dissociation of hydrogen peroxide, formed through water sonolysis, to hydroxyl radicals. Experiments in UPW spiked with an excess of tert-butanol (radical scavenger), sodium dodecyl sulfate or sodium acetate (surfactants) led to substantially decreased rates (i.e. by about 8 times), thus implying that the liquid bulk and the gas-liquid interface are major reaction sites. The stability of CX/CoFe was shown by performing reusability cycles employing magnetic separation of the catalyst after the treatment stage. It was found that the CX/CoFe catalyst can be reused in up to four successive cycles without noteworthy variation of the overall performance of the sonocatalytic process.

The Value of T1 Mapping Techniques in the Assessment of Myocardial Interstitial Fibrosis.

Cardiac fibrosis, characterized by net accumulation of extracellular matrix in the myocardium, is a common final pathway of heart failure. This myocardial fibrosis (MF) is not necessarily the primary cause of dysfunction; it often results from a reparative process activated in response to cardiomyocyte injury. In light of currently available treatments, late-identified MF could be definitive or irreversible, associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness and arrhythmia. T1 mapping should be used to detect incipient changes leading to myocardial damage in several clinical conditions and also in subclinical disease. This article reviews available techniques for MF detection, focusing on noninvasive quantification of diffuse fibrosis and clinical applications.

Multifunctional graphene-based magnetic nanocarriers for combined hyperthermia and dual stimuli-responsive drug delivery.

The synthesis of hydrophilic graphene-based yolk-shell magnetic nanoparticles functionalized with copolymer pluronic F-127 (GYSMNP@PF127) is herein reported to achieve an efficient multifunctional biomedical system for mild hyperthermia and stimuli-responsive drug delivery. In vitro tests revealed the extraordinary ability of GYSMNP@PF127 to act as smart stimuli-responsive multifunctional nanomedicine platform for cancer therapy, exhibiting (i) an outstanding loading capacity of 91% (w/w, representing 910 µg mg-1) of the chemotherapeutic drug doxorubicin, (ii) a high heating efficiency under an alternating (AC) magnetic field (intrinsic power loss ranging from 2.1-2.7 nHm2 kg-1), and (iii) a dual pH and thermal stimuli-responsive drug controlled release (46% at acidic tumour pH vs 7% at physiological pH) under AC magnetic field, in just 30 min. Additionally, GYSMNP@PF127 presents optimal hydrodynamic diameter (DH = 180 nm) with negative surface charge, high haemocompatibility for blood stream applications and tumour cellular uptake of drug nanocarriers. Due to its physicochemical, magnetic and biocompatibility properties, the developed graphene-based magnetic nanocarrier shows high promise as dual exogenous (AC field)/endogenous (pH) stimuli-responsive actuators for targeted thermo-chemotherapy, combining magnetic hyperthermia and controlled drug release triggered by the abnormal tumour environment. The presented strategy and findings can represent a new way to design and develop highly stable added-value graphene-based nanostructures for the combined treatment of cancer.

Independent and interactive effects of reduced seawater pH and oil contamination on subsurface sediment bacterial communities.

Ocean acidification may exacerbate the environmental impact of oil hydrocarbon pollution by disrupting the core composition of the superficial (0-1 cm) benthic bacterial communities. However, at the subsurface sediments (approximately 5 cm below sea floor), the local biochemical characteristics and the superjacent sediment barrier may buffer these environmental changes. In this study, we used a microcosm experimental approach to access the independent and interactive effects of reduced seawater pH and oil contamination on the composition of subsurface benthic bacterial communities, at two time points, by 16S rRNA gene-based high-throughput sequencing. An in-depth taxa-specific variance analysis revealed that the independent effects of reduced seawater pH and oil contamination were significant predictors of changes in the relative abundance of some specific bacterial groups (e.g., Firmicutes, Rhizobiales, and Desulfobulbaceae). However, our results indicated that the overall microbial community structure was not affected by independent and interactive effects of reduced pH and oil contamination. This study provides evidence that bacterial communities inhabiting subsurface sediment may be less susceptible to the effects of oil contamination in a scenario of reduced seawater pH.

Da diretriz ao mundo real: o papel dos inibidores de PCSK9 / From the guideline to the real world: the role of PCSK9 inhibitors

INTRODUÇÃO: A hipercolesterolemia é um fator de risco para aterosclerose. Segundo a Atualização brasileira de dislipidemias e prevenção de aterosclerose - 2017, a meta terapêutica de LDL colesterol (LDL-c) em pacientes com muito alto risco cardiovascular é menor que 50 mg/dL. OBJETIVO: Apresentar a porcentagem de pacientes de muito alto risco que atingiram as metas es-tabelecidas de LDL-c, tratados no ambulatório de dislipidemias de um hospital terciário, onde o acesso à atorvastatina é livre e gratuito e verificar indicação de prescrição de inibi-dores de PCSK9 de acordo com os critérios NICE (LDL-c >160). MÉTODO: Trata-se de um estudo transversal em que foram coletados dados de pacientes de muito alto risco cardiovascular - aterosclerose clinicamente manifesta, todos em uso de atorvastatina de 40 mg e 80 mg/dia, atendidos em um período de 60 dias no ano de 2018. RESULTADOS: Foram incluídos 280 pacientes, 62% do sexo masculino, média de idade foi de 66 (des-vio padrão 10) anos, 96% hipertensos, 86% diabéticos. Apenas 14% estavam com valor de LDL-c dentro da meta. Entre os que estavam fora da meta terapêutica, o LDL-c estava acima de 100 mg/ dL em 34% dos casos e acima de 160 mg/dL em 9%. CONCLUSÕES: Na prática clínica, a taxa de pacientes que atingem a meta terapêutica de LDL-c recomendada com o uso de estatina de alta potência é baixa. Segundo as recomendações do National Institute foi Health and Care Excellence (NICE), é indicado o uso inibidores de PCSK9 para pacientes de muito alto risco cardiovascular com hipercolesterolemia já em uso de estatina, mas que mantêm níveis de LDL acima de 160 mg/dL. Dessa forma, 9% dos pacientes fora da meta de LDL deste hospital terciário analisado poderiam se beneficiar do uso desses anticorpos monoclonais. (AU)

Degradation of propyl paraben by activated persulfate using iron-containing magnetic carbon xerogels: investigation of water matrix and process synergy effects.

An advanced oxidation process comprising an iron-containing magnetic carbon xerogel (CX/Fe) and persulfate was tested for the degradation of propyl paraben (PP), a contaminant of emerging concern, in various water matrices. Moreover, the effect of 20 kHz ultrasound or light irradiation on process performance was evaluated. The pseudo-first order degradation rate of PP was found to increase with increasing SPS concentration (25-500 mg/L) and decreasing PP concentration (1690-420 µg/L) and solution pH (9-3). Furthermore, the effect of water matrix on kinetics was detrimental depending on the complexity (i.e., wastewater, river water, bottled water) and the concentration of matrix constituents (i.e., humic acid, chloride, bicarbonate). The simultaneous use of CX/Fe and ultrasound as persulfate activators resulted in a synergistic effect, with the level of synergy (between 35 and 50%) depending on the water matrix. Conversely, coupling CX/Fe with simulated solar or UVA irradiation resulted in a cumulative effect in experiments performed in ultrapure water.

Activation of sodium persulfate by magnetic carbon xerogels (CX/CoFe) for the oxidation of bisphenol A: Process variables effects, matrix effects and reaction pathways.

An advanced oxidation process comprising sodium persulfate (SPS) and a novel magnetic carbon xerogel was tested for the degradation of bisphenol A (BPA), a model endocrine-disrupting compound. The catalyst, consisting of interconnected carbon microspheres with embedded iron and cobalt microparticles, was capable of activating persulfate to form sulfate and hydroxyl radicals at ambient conditions. The pseudo-first order degradation rate of BPA in ultrapure water (UPW) was found to increase with (i) increasing catalyst (25-75 mg/L) and SPS (31-250 mg/L) concentrations, (ii) decreasing BPA concentration (285-14,200 µg/L), and (iii) changing pH from alkaline to acidic values (9-3). Besides UPW, tests were conducted in drinking water, treated wastewater, groundwater and surface water; interestingly, the rate in UPW was always lower than in any other matrix containing several organic and inorganic constituents. The effect of natural organic matter (in the form of humic acids) and alcohols was detrimental to BPA degradation owing to the scavenging of radicals. Conversely, chlorides at concentrations greater than 50 mg/L had a positive effect due to the formation and subsequent participation of chlorine-containing radicals. Liquid chromatography time-of-flight mass spectrometry was employed to identify major transformation by-products (TBPs) of BPA degradation in the absence and presence of chlorides; in the latter case, several chlorinated TBPs were detected confirming the role of Cl-related radicals. Based on TBPs, main reaction pathways are proposed.

Identification of multienzymatic complexes in the Clonostachys byssicola secretomes produced in response to different lignocellulosic carbon sources.

Multienzymatic complexes with plant lignocellulose-degrading activities have recently been identified in filamentous fungi secretomes. Such complexes have potential biotechnological applications in the degradation of agro-industrial residues. Fungal species from the Clonostachys genus have been intensively investigated as biocontrol agents; however so far their use as producers of lignocellulose-degrading enzymes has not been extensively explored. Secretomes of Clonostachys byssicola following growth on different carbon sources (passion fruit peel, soybean hulls, cotton gin trash, banana stalk, sugarcane bagasse, orange peel, and a composition of soybean hulls: cotton gin trash:orange peel) were subjected to enzymatic assays. Remarkable differences were observed among the samples, especially regarding levels of mannanase and pectinase activities. Secretomes were then subjected to Blue Native PAGE in order to resolve putative protein complexes which subsequently had their composition revealed by trypsin digestion followed by LC-MS/MS analysis. The protein bands (named I, II, III and IV) were shown to be composed by holocellulolytic enzymes, mainly cellulases and xylanases as well as proteins involved in biocontrol processes, such as chitinases and proteases. The high diversity of proteins found in these multicatalytic assemblies confirms C. byssicola as a novel source of plant biomass-degrading enzymes.

Arritmias e classificação do risco de morte súbita em cardiopatias congênitas do adulto / Arrhythmias and classification of risk of sudden death in adult congenital heart diseases

Avanços no tratamento de crianças com cardiopatia congênita causou aumento dessa população em idade adulta, criando a necessidade de uma nova especialidade cardiológica: cardiopatia congênita em adulto...