Tailored electrochemical biosensor with poly-diallydimethylammonium chloride-functionalised multiwalled carbon nanotubes/gold nanoparticles/manganese dioxide, and haemoglobin for sensitive hydrogen peroxide detection.

A very sensitive electrochemical biosensor, with haemoglobin (Hb) as its basis, has been created to quantify hydrogen peroxide (H2O2), an essential marker in environmental monitoring, food safety, and medical diagnosis. The sensor uses a simple, eco-friendly preparation method. Hb was immobilised on manganese dioxide nanostructure/gold nanoparticles/poly-diallydimethylammonium chloride-functionalised multiwalled carbon nanotubes (PDDA-MWCNT/AuNP/MnO2), characterised using various techniques: amperometry, voltammetry, X-ray diffraction (XRD), and transmission electron microscopy (TEM). Nafion was used as a binder membrane to preserve the biological and electrochemical properties of the protein on the modified electrode. In comparison to earlier research, the novel biosensor had a lower detection limit (1.83 µM) and a limit of quantification (6.11 µM) (S/N = 3) for H2O2. It also exhibited notable reproducibility, long-term stability, and repeatability. It was effectively used to measure the amount of H2O2 in cow milk and orange juice, yielding recoveries in the order of 98.90-99.53 % with RSDs less than 5.0 %, which makes it a promising biosensor for food control.

Insights from Syzygium aromaticum Essential Oil: Encapsulation, Characterization, and Antioxidant Activity.

Alginate encapsulates loaded with clove essential oil (CEO) were prepared by ionic gelation, with subsequent freeze-drying. The objective of the present work was to develop a product with the ability to protect CEO against its easy volatility and oxidation. The following techniques were used to characterize the formulations: eugenol release, degree of swelling, GC/MS, TGA/DSC, and SEM. The alginate solution (1.0%) containing different concentrations of CEO (LF1: 1.0%; LF2: 0.5%; LF3: 0.1%) was dropped into a 3.0% CaCl2 solution. After lyophilization, the encapsulated samples were wrinkled and rigid, with high encapsulation power (LF3: 76.9% ± 0.5). Three chemical components were identified: eugenol (the major one), caryophyllene, and humulene. The antioxidant power (LF1: DPPH IC50 18.1 µg mL-1) was consistent with the phenol content (LF1: 172.2 mg GAE g-1). The encapsulated ones were thermally stable, as shown by analysis of FTIR peaks, eugenol molecular structure was kept unaltered. The degree of swelling was 19.2% (PBS). The release of eugenol (92.5%) in the PBS solution was faster than in the acidic medium. It was concluded that the low-cost technology used allows the maintenance of the content and characteristics of CEO in the three concentrations tested, offering a basis for further research with essential oil encapsulates.

E-Stilbenes: General Chemical and Biological Aspects, Potential Pharmacological Activity Based on the Nrf2 Pathway.

Stilbenes are phytoalexins, and their biosynthesis can occur through a natural route (shikimate precursor) or an alternative route (in microorganism cultures). The latter is a metabolic engineering strategy to enhance production due to stilbenes recognized pharmacological and medicinal potential. It is believed that in the human body, these potential activities can be modulated by the regulation of the nuclear factor erythroid derived 2 (Nrf2), which increases the expression of antioxidant enzymes. Given this, our review aims to critically analyze evidence regarding E-stilbenes in human metabolism and the Nrf2 activation pathway, with an emphasis on inflammatory and oxidative stress aspects related to the pathophysiology of chronic and metabolic diseases. In this comprehensive literature review, it can be observed that despite the broad number of stilbenes, those most frequently explored in clinical trials and preclinical studies (in vitro and in vivo) were resveratrol, piceatannol, pterostilbene, polydatin, stilbestrol, and pinosylvin. In some cases, depending on the dose/concentration and chemical nature of the stilbene, it was possible to identify activation of the Nrf2 pathway. Furthermore, the use of some experimental models presented a challenge in comparing results. In view of the above, it can be suggested that E-stilbenes have a relationship with the Nrf2 pathway, whether directly or indirectly, through different biological pathways, and in different diseases or conditions that are mainly related to inflammation and oxidative stress.

The role played by oral antioxidant therapies in preventing and treating preeclampsia: An updated meta-analysis.

AIMS: Performing an up-to-date meta-analysis of oral antioxidant therapies and determining whether they are effective in preventing and/or treating preeclampsia (PE). DATA SYNTHESIS: Search was performed in PubMed, CENTRAL, LILACS, Web of Science, and ScienceDirect databases. The risk of bias was assessed based on using Cochrane Collaboration's tool. A funnel plot was created, and Egger's and Peter's test was carried out to assess publication bias in the primary outcome of prevention studies. The overall quality of the evidence was assessed based on using the Grading of Recommendations Assessment, Developing and Evaluation (GRADE) tool; a formal protocol was published in the PROSPERO database (registration number CRD42022348992). In total, 32 studies were taken into consideration for analysis purposes; 22 studies focused on investigating preeclampsia prevention methods, whereas 10 focused on its treatment. Significant results associated with the incidence of preeclampsia were observed in prevention studies comprising 11,198 subjects and 1106 events in the control groups, as well as 11,156 subjects and 1048 events in the intervention groups (relative risk [RR]: 0.86, 95% confidence interval [CI]: [0.75, 0.99], P = 0.03; I2 = 44%, P = 0.02). With respect to outcomes associated with treatment studies, only intrauterine growth restriction has shown significant effects. Egger's and Peter's test has evidenced publication bias. Six outcomes in prevention studies were classified as having low quality and two as having moderate quality, whereas all three outcomes assessed in treatment studies were classified as having moderate quality. CONCLUSIONS: Antioxidant therapy has shown beneficial effects on preeclampsia prevention; moreover, the positive impact of this therapy on intrauterine growth restriction was observed during the disease treatment.

Extraction-assisted voltammetric determination of homocysteine using magnetic nanoparticles modified with molecularly imprinted polymer.

A magnetic graphite-epoxy composite (m-GEC) electrochemical sensor is presented based on magnetic imprinted polymer (mag-MIP) to determine homocysteine (Hcy). Mag-MIP was synthesized via precipitation polymerization, using functionalized magnetic nanoparticles (Fe3O4) together with the template molecule (Hcy), the functional monomer 2-hydroxyethyl methacrylate (HEMA), and the structural monomer trimethylolpropane trimethacrylate (TRIM). For mag-NIP (magnetic non-imprinted polymer), the procedure was the same in the absence of Hcy. Morphological and structural properties of the resultant mag-MIP and mag-NIP were examined using TEM, FT-IR, and Vibrating Sample Magnetometer. Under optimized conditions, the m-GEC/mag-MIP sensor showed a linear range of 0.1-2 µmol L-1, with a limit of detection (LOD) of 0.030 µmol L-1. In addition, the proposed sensor responded selectively to Hcy compared to several interferents present in biological samples. The recovery values determined by differential pulse voltammetry (DPV) were close to 100% for natural and synthetic samples, indicating good method accuracy. The developed electrochemical sensor proves to be a suitable device for determining Hcy, with advantages related to magnetic separation and electrochemical analysis.

Development of a Polymeric Membrane Impregnated with Poly-Lactic Acid (PLA) Nanoparticles Loaded with Red Propolis (RP).

The main objectives of this study were to develop and characterize hydrophilic polymeric membranes impregnated with poly-lactic acid (PLA) nanoparticles (NPs) combined with red propolis (RP). Ultrasonic-assisted extraction was used to obtain 30% (w/v) red propolis hydroalcoholic extract (RPE). The NPs (75,000 g mol-1) alone and incorporated with RP (NPRP) were obtained using the solvent emulsification and diffusion technique. Biopolymeric hydrogel membranes (MNPRP) were obtained using carboxymethylcellulose (CMC) and NPRP. Their characterization was performed using thermal analysis, Fourier transform infrared (FTIR), total phenols (TPC) and flavonoids contents (TFC), and antioxidant activity through the radical scavenging assay with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and Ferric reducing antioxidant power (FRAP). The identification and quantification of significant RP markers were performed through UPLC-DAD. The NPs were evaluated for particle size, polydispersity index, and zeta potential. The TPC for RPE, NPRP, and MNPRP was 240.3 ± 3.4, 191.7 ± 0.3, and 183.4 ± 2.1 mg EGA g-1, while for TFC, the value was 37.8 ± 0.9, 35 ± 3.9, and 26.8 ± 1.9 mg EQ g-1, respectively. Relevant antioxidant activity was also observed by FRAP, with 1400.2 (RPE), 1294.2 (NPRP), and 696.2 µmol Fe2+ g-1 (MNPRP). The primary markers of RP were liquiritigenin, isoliquiritigenin, and formononetin. The particle sizes were 194.1 (NPs) and 361.2 nm (NPRP), with an encapsulation efficiency of 85.4%. Thermal analysis revealed high thermal stability for the PLA, nanoparticles, and membranes. The DSC revealed no interaction between the components. FTIR allowed for characterizing the RPE encapsulation in NPRP and CMC for the MNPRP. The membrane loaded with NPRP, fully characterized, has antioxidant capacity and may have application in the treatment of skin wounds.

Antidiabetic, Antiglycation, and Antioxidant Activities of Ethanolic Seed Extract of Passiflora edulis and Piceatannol In Vitro.

The objective of this work was to investigate the antidiabetic, antiglycation, and antioxidant potentials of ethanolic extract of seeds of Brazilian Passiflora edulis fruits (PESE), a major by-product of the juice industry, and piceatannol (PIC), one of the main phytochemicals of PESE. PESE, PIC, and acarbose (ACB) exhibited IC50 for alpha-amylase, 32.1 ± 2.7, 85.4 ± 0.7, and 0.4 ± 0.1 µg/mL, respectively, and IC50 for alpha-glucosidase, 76.2 ± 1.9, 20.4 ± 7.6, and 252 ± 4.5 µg/mL, respectively. The IC50 of PESE, PIC, and sitagliptin (STG) for dipeptidyl-peptidase-4 (DPP-4) was 71.1 ± 2.6, 1137 ± 120, and 0.005 ± 0.001 µg/mL, respectively. PESE and PIC inhibited the formation of advanced glycation end-products (AGE) with IC50 of 366 ± 1.9 and 360 ± 9.1 µg/mL for the initial stage and 51.5 ± 1.4 and 67.4 ± 4.6 µg/mL for the intermediate stage of glycation, respectively. Additionally, PESE and PIC inhibited the formation of ß-amyloid fibrils in vitro up to 100%. IC50 values for 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•) scavenging activity of PESE and PIC were 20.4 ± 2.1, and 6.3 ± 1.3 µg/mL, respectively. IC50 values for scavenging hypochlorous acid (HOCl) were similar in PESE, PIC, and quercetin (QCT) with values of 1.7 ± 0.3, 1.2 ± 0.5, and 1.9 ± 0.3 µg/mL, respectively. PESE had no cytotoxicity to the human normal bronchial epithelial (BEAS-2B), and alpha mouse liver (AML-12) cells up to 100 and 50 µg/mL, respectively. However, 10 µg/mL of the extract was cytotoxic to non-malignant breast epithelial cells (MCF-10A). PESE and PIC were found to be capable of protecting cultured human cells from the oxidative stress caused by the carcinogen NNKOAc at 100 µM. The in vitro evidence of the inhibition of alpha-amylase, alpha-glucosidase, and DPP-4 enzymes as well as antioxidant and antiglycation activities, warrants further investigation of the antidiabetic potential of P. edulis seeds and PIC.

Monocyclic Nitro-heteroaryl Nitrones with Dual Mechanism of Activation: Synthesis and Antileishmanial Activity.

5-Nitro-furan nitrones (1) and 5-nitro-thiophene nitrones (2) were synthesized in one step. Compounds 1a-c had the most potent leishmanicidal activity against intracellular amastigote forms of Leishmania amazonensis and L. infantum (from 0.019 to 2.76 µM), with excellent selectivity (from 39 to 5673). The comparison of the leishmanicidal activity in promastigotes of wild type L. donovani with those overexpressing nitroreductases NRT1 or NRT2 shows that 1a,b are activated by both, which could slow the development of resistance. Their redox potential (E redox) obtained by cyclic voltammetry (-0.67 and -0.62 V) shows that the reduction of the nitro group is modulated by the nitrone group. Oral administration of 1b to mice infected by L. infantum reduced the parasite load on the spleen by 76.6 and 95.0% with doses of 50 and 100 mg/kg, respectively, administered twice a day, for 5 days. In the liver, the parasite load suppression was above 75% with either treatment.

New Insights for Red Propolis of Alagoas-Chemical Constituents, Topical Membrane Formulations and Their Physicochemical and Biological Properties.

The main objectives of this study were to evaluate the chemical constitution and allergenic potential of red propolis extract (RPE). They were evaluated, using high performance liquid chromatography (HPLC) and the release of ß-hexosaminidase, respectively. A plethora of biologically active polyphenols and the absence of allergic responses were evinced. RPE inhibited the release of ß-hexosaminidase, suggesting that the extract does not stimulate allergic responses. Additionally, the physicochemical properties and antibacterial activity of hydrogel membranes loaded with RPE were analyzed. Bio-polymeric hydrogel membranes (M) were obtained using 5% carboxymethylcellulose (M1 and M2), 1.0% of citric acid (M3) and 10% RPE (for all). Their characterization was performed using thermal analysis, Fourier transform infrared (FTIR), total phenolic content, phenol release test and, antioxidant activity through 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and Ferric Reducing Antioxidant Power (FRAP). The latter appointed to the similar antioxidant capacity of the M1, M2 and M3. The degradation profiles showed higher thermostability to M3, followed by M2 and M1. The incorporation of RPE into the matrices and the crosslinking of M3 were evinced by FTIR. There were differences in the release of phenolic compounds, with a higher release related to M1 and lower in the strongly crosslinked M3. The degradation profiles showed higher thermostability to M3, followed by M2 and M1. The antibacterial activity of the membranes was determined using the disc diffusion assay, in comparison with controls, obtained in the same way, without RPE. The membranes elicited antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis, with superior performance over M3. The hydrogel membranes loaded with RPE promote a physical barrier against bacterial skin infections and may be applied in the wound healing process.

Schinus terebenthifolius Raddi extracts: From sunscreen activity toward protection of the placenta to Zika virus infection, new uses for a well-known medicinal plant.

Schinus terebinthifolius Raddi is a well-known medicinal plant native of South America. This species has demonstrated important biological activities such as antihypertensive and vasodilator, antimicrobial, anti-inflammatory and antioxidant. However, no studies have been, so far, reported with the fruits of S. terebinthifolius as a protector of the placenta against Zika virus infection and as sunscreen agents. The present study aimed to investigate new uses for the ethanolic fruit extracts of S. terebinthifolius, from fruits'peel (STPE) and from the whole fruits (STWFE). Zika virus (ZIKV) has been linked to several fetal malformations, such as microcephaly and other central nervous system abnormalities. Thus, the potential of these natural extracts against ZIKV infection was evaluated, using an in vitro method. The photoprotective potential, determined by spectrometry, along with phenolic content, antioxidant capacity, and chemical composition of both extracts were also evaluated. The chemical composition of the extracts was evaluated by HPLC-UV / vis. The cytotoxicity of peel and whole fruit extracts in vero E6 cell lines, in placental cell lines and placental explant cultures were evaluated by the MTT assay. The infectivity of placental cells and explants was evaluated by qRT-PCR and the effects of extracts on ZIKV infection were investigated using HTR-8/SVneo cells, pre-treated with 100 µg mL-1 of STWFE for 1 h, and infected with MR766 (AD) or PE243 (EH) ZIKV strains. STFE and STWFE were well-tolerated by both placental-derived trophoblast cell line HTR-8/SVneo as well as by term placental chorionic villi explants, which indicate absence of cytotoxicity in all analysed concentrations. Two strains of ZIKV were tested to access if pre-treatment of trophoblast cells with the STWFE would protect them against infection. Flow cytometry analysis revealed that STWFE extract greatly reduced ZIKV infection. The extracts were also photoprotective with SPF values equivalent to the standard, benzophenone-3. The formulations prepared in different concentrations of the extracts (5-10 %) had shown maximum SPF values of 32.21. STWFE represents a potential natural mixture to be used in pregnancy in order to restrain placental infection by ZIKV and might potentially protect fetus against ZIKV-related malformations. The extracts exhibited photoprotective activity and some of the phenolic compounds, mainly resveratrol, catechin and epicatechin, are active ingredients in all assayed activities. The development of biotechnological/medical products, giving extra value to products from family farming, is expected, with strong prospects for success.

Synthesis of quinone imine and sulphur-containing compounds with antitumor and trypanocidal activities: redox and biological implications.

Ortho-Quinones represent a special class of redox active compounds associated with a spectrum of pronounced biological activities, including selective cytotoxicity and antimicrobial actions. The modification of the quinone ring by simple nitrogen and sulphur substitutions leads to several new classes of compounds with their own, distinct redox behaviour and equally distinct activities against cancer cell lines and Trypanosoma cruzi. Some of the compounds investigated show activity against T. cruzi at concentrations of 24.3 and 65.6 µM with a selectivity index of around 1. These results demonstrate that simple chemical modifications on the ortho-quinone ring system, in particular, by heteroatoms such as nitrogen and sulphur, transform these simple redox molecules into powerful cytotoxic agents with considerable "potential", not only in synthesis and electrochemistry, but also, in a broader sense, in health sciences.

Hyperferritinemia worsens the perinatal outcomes of conceptions of pregnancies with preeclampsia.

BACKGROUND AND AIMS: To analyze the prevalence of hyperferritinemia in pregnant women with preeclampsia and its association with adverse perinatal outcomes. METHODS: A cross-sectional study carried out in 2017 with a convenience sample of pregnant women with preeclampsia attended at a high-risk maternity hospital in Alagoas, Brazil. Socioeconomic, lifestyle, clinical and biochemical data were collected through a structured questionnaire. Type of delivery, gestational age, weight and length at birth, and Apgar score were analyzed as outcome variables. Women were dichotomized according to the serum ferritin level (150 ng/mL). Poisson regression models were used to analyze the effect of hyperferritinemia on the outcome variables. Estimates were presented as prevalence ratio with 95% confidence intervals (PR [95% CI]). RESULTS: Based on the Fisher's exact statistical teste and in the proportions of the neonatal outcome (birth weight), with a statistical significance of 5%, the statistical power of the sample studied was 83%. Two hundred six pregnant women with preeclampsia were recruited, which 8.74% presented hyperferritinemia. Except for ferritin level, there were no differences in C-reactive protein (CRP), hemoglobin, Glutamate Oxaloacetate Transaminase (GOT) and Pyruvic Glutamic Transaminase (PGT) levels between women with or without hyperferritinemia. After adjusting for potential confounders, hyperferritinemia was associated with low birth weight (2.19 [2.13-3.89 95%CI]), low birth length (7.76 [2.52-23.8 95% CI]) and being born small for gestational age (3.14 [1.36-7.28 95% CI]). CONCLUSION: In the presence of hyperferritinemia, preeclampsia patients were associated with a higher rate of unfavorable neonatal outcomes.

Mitochondrial disfunction and ROS production are essential for anti-Trypanosoma cruzi activity of ß-lapachone-derived naphthoimidazoles.

Chagas disease is caused by the hemoflagellate protozoa Trypanosoma cruzi and is one of the most important neglected tropical diseases, especially in Latin American countries, where there is an association between low-income populations and mortality. The nitroderivatives used in current chemotherapy are far from ideal and present severe limitations, justifying the continuous search for alternative drugs. Since the1990s, our group has been investigating the trypanocidal activity of natural naphthoquinones and their derivatives, and three naphthoimidazoles (N1, N2 and N3) derived from ß-lapachone were found to be most effective in vitro. Analysis of their mechanism of action via cellular, molecular and proteomic approaches indicates that the parasite mitochondrion contains one of the primary targets of these compounds, trypanothione synthetase (involved in trypanothione production), which is overexpressed after treatment with these compounds. Here, we further evaluated the participation of the mitochondria and reactive oxygen species (ROS) in the anti-T. cruzi action of naphthoimidazoles. Preincubation of epimastigotes and trypomastigotes with antioxidants (α-tocopherol and urate) strongly protected the parasites from the trypanocidal effect of naphthoimidazoles, decreasing the ROS levels produced and reverting the mitochondrial swelling phenotype. The addition of pro-oxidants (menadione and H2O2) before the treatment induced an increase in parasite lysis. Despite the O2 uptake and mitochondrial complex activity being strongly reduced by N1, N2 and N3, urate partially restored the mitochondrial metabolism only in N1-treated parasites. In parallel, MitoTEMPO, a mitochondrial-targeted antioxidant, protected the functionality of the mitochondria in N2- and N3-treated parasites. In addition, the trypanothione reductase activity was remarkably increased after treatment with N1 and N3, and molecular docking demonstrated that these two compounds were positioned in pockets of this enzyme. Based on our findings, the direct impairment of the mitochondrial electron transport chain by N2 and N3 led to an oxidative misbalance, which exacerbated ROS generation and led to parasite death. Although other mechanisms cannot be discounted, mainly in N1-treated parasites, further investigations are required.

Direct sequential C-H iodination/organoyl-thiolation for the benzenoid A-ring modification of quinonoid deactivated systems: a new protocol for potent trypanocidal quinones.

We report a sequential C-H iodination/organoyl-thiolation of naphthoquinones and their relevant trypanocidal activity. Under a combination of AgSR with a copper source, sulfur-substituted benzenoid quinones were prepared in high yields (generally >90%). This provides an efficient and general method for preparing A-ring modified naphthoquinoidal systems, recognized as a challenge in quinone chemistry.

Rhodium-catalyzed C-H bond activation for the synthesis of quinonoid compounds: Significant Anti-Trypanosoma cruzi activities and electrochemical studies of functionalized quinones.

Thirty four halogen and selenium-containing quinones, synthesized by rhodium-catalyzed C-H bond activation and palladium-catalyzed cross-coupling reactions, were evaluated against bloodstream trypomastigotes of T. cruzi. We have identified fifteen compounds with IC50/24 h values of less than 2 µM. Electrochemical studies on A-ring functionalized naphthoquinones were also performed aiming to correlate redox properties with trypanocidal activity. For instance, (E)-5-styryl-1,4-naphthoquinone 59 and 5,8-diiodo-1,4-naphthoquinone 3, which are around fifty fold more active than the standard drug benznidazole, are potential derivatives for further investigation. These compounds represent powerful new agents useful in Chagas disease therapy.

Application of a nanostructured platform and imprinted sol-gel film for determination of chlorogenic acid in food samples.

Chlorogenic acid (CGA) is a polyphenol derivative that widely exists in higher plants like fruits, vegetables, black teas, and some traditional Chinese medicines. In this work, we have proposed a sensitive and selective electrochemical sensor for detection of CGA. The sensor was based on a glassy carbon electrode (GCE) modified with a functional platform by grafting vinyltrimethoxysilane (VTMS) in multi-walled carbon nanotubes (MWCNTs) and covered by a molecularly imprinted siloxane (MIS) film prepared using the sol-gel process. The VTMS was grafted onto the surface of the MWCNTs via in situ free radical polymerization. The MIS was obtained from the acid-catalyzed hydrolysis/condensation of a solution consisting of tetraethoxysilane (TEOS), phenyltriethoxysilane (PTEOS), (3-aminopropyl)trimethoxysilane (APTMS), and CGA as a template molecule. The modification procedure was evaluated by differential pulse voltammetry (DPV) and scanning electron microscopy (SEM). Under optimized operational conditions, a linear response was obtained covering a concentration ranging from 0.08µmolL(-1) to 500µmolL(-1) with a detection limit (LOD) of 0.032µmolL(-1). The proposed sensor was applied to CGA determination in coffee, tomato, and apple samples with recoveries ranging from 99.3% to 108.6%, showing a promising potential application in food samples. Additionally, the imprinted sensor showed a significantly higher affinity for target CGA than the non-imprinted siloxane (NIS) sensor.

Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-α, and IL-1ß.

This study aims to evaluate the effects of diets deficient in choline and/or cystine on hepatocellular injury in animal models (young male Wistar rats, aged 21 days), by monitoring some of the oxidative stress biomarkers and the expression of RAGE, TNF-α, and IL-1ß. The animals were divided into 6 groups (n = 10) and submitted to different diets over 30 days: AIN-93 diet (standard, St), AIN-93 choline deficient (CD) diet and AIN-93 choline and cystine deficient (CCD) diet, in the pellet (pl) and powder (pw) diet forms. Independently of the diet form, AIN-93 diet already led to hepatic steatosis and CD/CCD diets provoked hepatic damage. The increase of lipid peroxidation, represented by the evaluation of thiobarbituric acid reactive species, associated with the decrease of levels of antioxidant enzymes, were the parameters with higher significance toward redox profile in this model of hepatic injury. Regarding inflammation, in relation to TNF-α, higher levels were evidenced in CD(pl), while, for IL-1ß, no significant alteration was detected. RAGE expression was practically the same in all groups, with exception of CCD(pw) versus CCD(pl). These results together confirm that AIN-93 causes hepatic steatosis and choline and/or cysteine deficiencies produce important hepatic injury associated with oxidative stress and inflammatory profiles.

Arginase as a Critical Prooxidant Mediator in the Binomial Endothelial Dysfunction-Atherosclerosis.

Arginase is a metalloenzyme which hydrolyzes L-arginine to L-ornithine and urea. Since its discovery, in the early 1900s, this enzyme has gained increasing attention, as literature reports have progressively pointed to its critical participation in regulating nitric oxide bioavailability. Indeed, accumulating evidence in the following years would picture arginase as a key player in vascular health. Recent studies have highlighted the arginase regulatory role in the progression of atherosclerosis, the latter an essentially prooxidant state. Apart from the fact that arginase has been proven to impair different metabolic pathways, and also as a consequence of this, the repercussions of the actions of such enzyme go further than first thought. In fact, such metalloenzyme exhibits direct implications in multiple cardiometabolic diseases, among which are hypertension, type 2 diabetes, and hypercholesterolemia. Considering the epidemiological repercussions of these clinical conditions, arginase is currently seen under the spotlights of the search for developing specific inhibitors, in order to mitigate its deleterious effects. That said, the present review focuses on the role of arginase in endothelial function and its participation in the establishment of atherosclerotic lesions, discussing the main regulatory mechanisms of the enzyme, also highlighting the potential development of pharmacological strategies in related cardiovascular diseases.

Selective endocytic trafficking in live cells with fluorescent naphthoxazoles and their boron complexes.

Fluorescent naphthoxazoles and their boron derivatives have been synthesized and applied as superior and selective probes for endocytic pathway tracking in live cancer cells. The best fluorophores were compared with the commercially available acridine orange (co-staining experiments), showing far better selectivity.