Cupuaçu (Theobroma grandiflorum): A Multifunctional Amazonian Fruit with Extensive Benefits.

The Amazon region is known for its continental dimension, water abundance, and especially for the rich biodiversity that this biome hosts. Among the thousands of plant species in the Amazon, many represent food sources. Among these, cupuaçu (Theobroma grandiflorum (Willd. ex Spreng.) K.Schum.) stands out as an iconic fruit with an exotic flavor, appreciated for its remarkable organoleptic properties. The present review aims to provide a comprehensive description of its biology, agronomical uses, nutritional values, chemical compositions, medicinal properties, and industrial applications. The search based on scientific articles demonstrates T. grandiflorum as a valuable ingredient for the food, cosmetic and pharmaceutical sectors. Data analysis demonstrates that cupuaçu cultivation and processing contribute to the strengthening of local production chains and promotes the development of small communities, and thus the bioeconomy in the Amazon region. In this sense, since the last decade, cultivar improvement has required multidisciplinary efforts, resulting in disease-resistant plants with better productivity. Regarding its chemical composition, T. grandiflorum is a notable source of methylxanthine alkaloids, polyphenols, aroma compounds, and lipids. The presence of these compounds supports the use of cupuaçu in various products and help us to understand the potential health benefits of its consumption. Through the integration of all collected information, key gaps in basic and applied sciences were observed, highlighting the need for more research to uncover novel applications and products of T. grandiflorum. The development of new products based on biodiversity is fundamental to promoting environmental and economic sustainability, which are key steps to the survival of the Amazon rainforest. Therefore, this work summarizes the knowledge on this source and sheds light on a food source that is little known outside of the Amazon borders.

Genomic analysis of Oceanotoga teriensis strain UFV_LIMV02, a multidrug-resistant thermophilic bacterium isolated from an offshore oil reservoir.

Bacteria of the species Oceanotoga teriensis belong to the family Petrotogaceae, are Gram-negative bacilli, are moderately thermophilic and are included in the group of thiosulfate-reducing bacteria, being capable of significantly accelerating corrosion in metallic structures. However, no in-depth study on the genome, antibiotic resistance and mobile elements has been carried out so far. In this work, the isolation, phenotypic and genotypic characterization of the multi-resistant O. teriensis UFV_LIMV02 strain was carried out, from water samples from an offshore oil extraction platform in Rio de Janeiro (Brazil). We determined that the isolate has a genome of 2 812 778 bp in size, with 26 % GC content, organized into 34 contigs. Genomic annotation using Rapid Annotation using Subsystem Technology revealed the presence of genes related to resistance to antibiotics and heavy metals. By evaluating the antimicrobial resistance of the isolate using the disc diffusion technique, resistance was verified for the classes of antibiotics, beta-lactams, fluoroquinolones, aminoglycosides, sulfonamides, lincosamides and rifamycins, a total of 14 antibiotics. The search for genomic islands, prophages and defence systems against phage infection revealed the presence of five genomic islands in its genome, containing genes related to resistance to heavy metals and antibiotics, most of which are efflux pumps and several transposases. No prophage was found in its genome; however, nine different defence systems against phage infection were detected. When analysing the clustered regularly interspaced short palindromic repeat (CRISPR) systems, four CRISPR arrays, classified as types I-B and III-B, with 272 spacers, can provide the strain with immunity to different mobile genetic elements and bacteriophage infection. The results found in this study show that the isolate UFV_LIVM02 is an environmental bacterium, resistant to different classes of antibiotics, and that the proteins encoded by the predicted genomic islands may be associated with the development of greater resistance to antibiotics and heavy metals. They provide evidence that environmental bacteria found in offshore oil exploration residues may pose a risk for the spread of antibiotic resistance genes. More comprehensive studies on the microbial community present in oil waste are needed to assess the risks of horizontal gene transfer.

Structural analysis and shape-based identification of novel inhibitors targeting the Trypanosoma cruzi proteasome.

There is an urgent need to develop new, safer, and more effective drugs against Chagas disease (CD) as well as related kinetoplastid diseases. Targeting and inhibiting the Trypanosoma cruzi proteasome has emerged as a promising therapeutic approach in this context. To expand the chemical space for this class of inhibitors, we performed virtual screening campaigns with emphasis on shape-based similarity and ADMET prioritization. We describe the ideation and application of robustly validated shape queries for these campaigns, which furnished 44 compounds for biological evaluation. Five hit compounds demonstrated in vitro antitrypanosomal activity by potential inhibition of T. cruzi proteasome and notable chemical diversities, particularly, LCQFTC11. Structural insights were achieved by homology modeling, sequence/structure alignment, proteasome-species comparison, docking, molecular dynamics, and MMGBSA binding affinity estimations. These methods confirmed key interactions as well as the stability of LCQFTC11 at the ß4/ß5 subunits' binding site of the T. cruzi proteasome, consistent with known inhibitors. Our results warrant future assay confirmation of our hit as a T. cruzi proteasome inhibitor. Importantly, we also shed light into dynamic details for a proteasome inhibition mechanism that shall be further investigated. We expect to contribute to the development of viable CD drug candidates through such a relevant approach.

New records of helminth infections in Bothrops atrox Linnaeus, 1758 from Marajó Island-Brazil and a literature review with a check list of helminths infecting Bothrops species (Squamata, Viperidae) in the neotropical region.

Snakes of the genus Bothrops inhabit tropical forests in Central and South America and are important for the biomedical and pharmaceutical industries because of the chemical properties of their venom. They serve as either definitive or intermediate hosts for many parasitic helminths. The Marajó Island (Brazil) is the natural habitat of venomous snakes, Bothrops atrox and Bothrops marajoensis, which are often found around rural and peri-urban areas and are known to bite humans. Samples of helminths parasitizing the oral cavity, subcutaneous tissues, coelomic cavity, and intestine of four B. atrox from Marajó Island (Pará-Brazil) were collected. The specimens studied were taxonomically classified as trematodes of the species Stycholecitha serpentis, nematodes of the genera Eustrongylides and Camallanus and cystacanths of an acanthocephalan of the genus Centrorhynchus. The aims of the present study were: to record helminths found in B. atrox from the Marajó Island; to discuss their role as definitive, intermediate, or paratenic hosts; and to compile a list of helminths that have been recorded in snakes of the genus Bothrops of the Neotropical region.

Prospecting Specific Protein Patterns for High Body Mass Index (BMI), Metabolic Syndrome and Type 2 Diabetes in Saliva and Blood Plasma From a Brazilian Population.

PURPOSE: Obesity and its associated metabolic disorders, such as T2DM and MeS, are a growing public health problem worldwide. Our goal was the identification of protein patterns that are uniquely characteristic of higher BMI, MeS, and T2DM in a Brazilian population. EXPERIMENTAL DESIGN: Saliva and plasma proteomes, clinical parameters were analyzed in a population from the state of Rio de Janeiro, Brazil, a mixed-race population. Volunteers were sorted by their BMI into normal (n = 29), overweight (n = 25), and obese (n = 15) and were compared with individuals with MeS (n = 23) and T2DM (n = 11). RESULTS: The Random Forest (RF) predictive model revealed that three clinical variables, BMI, HOMA-IR, and fasting blood glucose, are most important for predicting MeS and T2DM. A total of six plasmatic proteins (ABCD4, LDB1, PDZ, podoplanin, lipirin-alpha-3, and WRS) and six salivary proteins (hemoglobin subunit beta, POTEE, T cell receptor alpha variable 9-2, lactotransferrin, cystatin-S, carbonic anhydrase 6), are enhanced in T2DM and in MeS. CONCLUSIONS AND CLINICAL RELEVANCE: Our data revealed similar alterations in protein composition across individuals with abnormal weight gain, T2DM, and MeS. This finding confirms the close link between these conditions at the molecular level in the studied population, potentially enhancing our understanding of these diseases and paving the way for the development of novel diagnostic tools.

Generalized scaling laws for the irrotational motions bordering a turbulent region.

In turbulent free shear flows such as jets and wakes, and also in turbulent boundary layers, the turbulent region is bounded by a region of irrotational flow where the magnitude of the potential velocity fluctuations can be very high. This is particularly true close to the turbulent-nonturbulent interface layer (TNTI) that separates the regions of turbulent (rotational) and nonturbulent (irrotational) fluid motion in these flows. Previous works have shown that for distances from the TNTI x_{2} much bigger than the integral scale L in the nearby turbulent region (x_{2}≫L), the variance of the velocity fluctuations 〈u_{i}^{2}〉 (i=1,2,3) depends on the shape of the kinetic energy spectrum in the infrared region E(k)∼k^{n} [O. M. Phillips, Proc. Camb. Phil. Soc. 51, 220 (1955)10.1017/S0305004100030073; Xavier et al., J. Fluid Mech. 918, A3 (2021)10.1017/jfm.2021.296]. Using rapid distortion theory, we derive the generalized scaling laws for the potential velocity fluctuations, at distances sufficiently far from the TNTI layer, for any value of n. While the cases n=4 (Batchelor turbulence) and n=2 (Saffman turbulence) have been previously derived, with 〈u_{i}^{2}〉∼x_{2}^{-4} and 〈u_{i}^{2}〉∼x_{2}^{-3}, for n=4 and n=2, respectively [O. M. Phillips, Proc. Camb. Phil. Soc. 51, 220 (1955)10.1017/S0305004100030073; Xavier et al., J. Fluid Mech. 918, A3 (2021)10.1017/jfm.2021.296.], we extend these results by including any other value of n. In particular, we obtain 〈u_{i}^{2}〉∼x_{2}^{-2} and 〈u_{i}^{2}〉∼x_{2}^{-4}, for n=1 and n≥5, respectively, while n=3 yields 〈u_{i}^{2}〉∼x_{2}^{-4}ln(x_{2}). These theoretical results are confirmed by direct numerical simulations of turbulent fronts evolving into an irrotational flow region in the absence of mean shear.

LMI-Based MPC Design Applied to the Single-Phase PWM Inverter with LC Filter under Uncertain Parameters.

This work proposes a design methodology for predictive control applied to the single-phase PWM inverter with an LC filter. In the design, we considered that the PWM inverter has parametric uncertainties in the filter inductance and output load resistance. The control system purpose is to track a sinusoidal signal at the inverter output. The designed control system with an embedded integrator uses the principle of receding horizon control, which underpinned predictive control. The methodology was described by linear matrix inequalities, which can be solved efficiently using convex programming techniques, and the optimal solution is obtained. MATLAB-Simulink and real-time FPGA-in-the-loop simulations illustrate the viability of the proposed control system. The LMI-based MPC reveals an effective performance for tracking of a sinusoidal reference signal and disturbance rejection of input voltage and load perturbations for the inverter subject to uncertainties.

NONO2P, a novel nitric oxide donor, causes vasorelaxation through NO/sGC/PKG pathway, K+ channels opening and SERCA activation.

BACKGROUND & AIMS: The treatment of cardiovascular diseases (CVD) could greatly benefit from using nitric oxide (NO) donors. This study aimed to investigate the mechanisms of action of NONO2P that contribute to the observed responses in the mesenteric artery. The hypothesis was that NONO2P would have similar pharmacological actions to sodium nitroprusside (SNP) and NO. METHODS: Male Wistar rats were euthanized to isolate the superior mesenteric artery for isometric tension recordings. NO levels were measured using the DAF-FM/DA dye, and cyclic guanosine monophosphate (cGMP) levels were determined using a cGMP-ELISA Kit. RESULTS: NONO2P presented a similar maximum efficacy to SNP. The free radical of NO (NO•) scavengers (PTIO; 100 µM and hydroxocobalamin; 30 µM) and nitroxyl anion (NO-) scavenger (L-cysteine; 3 mM) decreased relaxations promoted by NONO2P. The presence of the specific soluble guanylyl cyclase (sGC) inhibitor (ODQ; 10 µM) nearly abolished the vasorelaxation. The cGMP-dependent protein kinase (PKG) inhibition (KT5823; 1 µM) attenuated the NONO2P relaxant effect. The vasorelaxant response was significantly attenuated by blocking inward rectifying K+ channels (Kir), voltage-operated K+ channels (KV), and large conductance Ca2+-activated K+ channels (BKCa). NONO2P-induced relaxation was attenuated by cyclopiazonic acid (10 µM), indicating that sarcoplasmic reticulum Ca2+-ATPase (SERCA) activation is involved in this relaxation. Moreover, NONO2P increased NO levels in endothelial cells and cGMP production. CONCLUSIONS: NONO2P induces vasorelaxation with the same magnitude as SNP, releasing NO• and NO-. Its vasorelaxant effect involves sGC, PKG, K+ channels opening, and SERCA activation, suggesting its potential as a therapeutic option for CVD.

Design of Promising Thiazoloindazole-Based Acetylcholinesterase Inhibitors Guided by Molecular Docking and Experimental Insights.

Alzheimer's disease is characterized by a progressive deterioration of cognitive function and memory loss, and it is closely associated with the dysregulation of cholinergic neurotransmission. Since acetylcholinesterase (AChE) is a critical enzyme in the nervous system, responsible for breaking down the neurotransmitter acetylcholine, its inhibition holds a significant interest in the treatment of various neurological disorders. Therefore, it is crucial to develop efficient AChE inhibitors capable of increasing acetylcholine levels, ultimately leading to improved cholinergic neurotransmission. The results reported here represent a step forward in the development of novel thiazoloindazole-based compounds that have the potential to serve as effective AChE inhibitors. Molecular docking studies revealed that certain of the evaluated nitroindazole-based compounds outperformed donepezil, a well-known AChE inhibitor used in Alzheimer's disease treatment. Sustained by these findings, two series of compounds were synthesized. One series included a triazole moiety (Tl45a-c), while the other incorporated a carbazole moiety (Tl58a-c). These compounds were isolated in yields ranging from 66 to 87% through nucleophilic substitution and Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reactions. Among the synthesized compounds, the thiazoloindazole-based 6b core derivatives emerged as selective AChE inhibitors, exhibiting remarkable IC50 values of less than 1.0 µM. Notably, derivative Tl45b displays superior performance as an AChE inhibitor, boasting the lowest IC50 (0.071 ± 0.014 µM). Structure-activity relationship (SAR) analysis indicated that derivatives containing the bis(trifluoromethyl)phenyl-triazolyl group demonstrated the most promising activity against AChE, when compared to more rigid substituents such as carbazolyl moiety. The combination of molecular docking and experimental synthesis provides a suitable and promising strategy for the development of new efficient thiazoloindazole-based AChE inhibitors.

Occurrence of parasitism promoted by Myzobdella lugubris Leidy, 1851 (Annelida: Piscicolidae) in Callinectes bocourti (Crustacea: Portunidae): A report of invasive leech in Brazilian Amazon province.

This study reports the presence of high parasitic load by Myzobdella lugubris Leidy, 1851 in the swimming crab Callinectes bocourti A. Milne-Edwards, 1879 from Amazon mangrove. We sampled the swimming crabs using a baited trap, between January and June 2023, in Santa Maria River, located in the municipality of Curuçá, state of Pará, Brazil (geographical coordinates 0°40'3.705"S, 047°54'43.405"W). After sampling, each swimming crab was individually placed in plastic containers for the count of leeches per individual. In the laboratory, the specimens were sexed, measured (parasite and host) and fixed in 70% alcohol. For the leech species identification, macroscopic techniques were combined with light microscopy (LM) and scanning electron microscopy (SEM). We examined 86 specimens of C. bocourti (75 males and 11 females) in a ratio of 1 M:0.14 F, all infested with leeches. In total, 186 leech specimens were collected, ranging from 1 to 21 leeches per host. Leeches oviposited the cocoons in greater quantities in ventral area of swimming crab carapace (32%), followed by dorsal area of carapace (29.09%), chelipeds (24.34%) and ambulatory legs (14.57%). The presence of M. lugubris is a risk to the health of the host, once it may transmit a range of diseases to aquatic organisms, and subsequently risk to human health.

Racial Disparities in Medication Use During Pregnancy: Results from the NISAMI Cohort.

Purpose: This study aimed to evaluate racial disparities in medication use and associated factors among pregnant women receiving prenatal care at Brazilian Unified Health System primary care health units in the northeast region. Patients and Methods: A total of 1058 pregnant women in the NISAMI Cohort were interviewed between June 2012 and February 2014. Medicines used during pregnancy were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and ANVISA pregnancy risk categories. Prevalence ratios (crude and adjusted) and 95% confidence intervals (CIs) were estimated using Poisson regression with robust error variance. All analyses were stratified by race (Asian, black, brown/mixed, Brazilian indigenous, and white). Results: Approximately 84% of the pregnant women used at least one medication, with a lower proportion among white women. The most reported medications were antianemic preparations (71.08%; 95% CI 68.27-73.72%), analgesics (21.74%; 95% CI 19.36-24.32%), and drugs for functional gastrointestinal disorders (18.81%; 95% CI 16.57-21.28%). Approximately 29% of women took potentially risky medications during pregnancy, with a higher prevalence among Asian and white women. Factors associated with medication use during pregnancy include a greater number of prenatal consultations, higher education levels, health problems, and smoking. In addition, maternal age above 25 years, smoking status, and two or more previous pregnancies were associated with potentially risky medication use during pregnancy. Conclusion: A high prevalence of medication use during pregnancy was found; however, this prevalence was lower among white women. Nonetheless, black and brown women used antianemic preparations less frequently. This finding suggests that race is a factor of inequity in prenatal care, demanding public policies to mitigate it.

Electrophysiological Properties and Morphology of Cardiac and Pulmonary Motoneurons within the Dorsal Motor Nucleus of the Vagus of Rats.

The dorsal motor nucleus of the vagus (DMV) contains parasympathetic motoneurons that project to the heart and lungs. These motoneurons control ventricular excitability/contractility and airways secretions/blood flow, respectively. However, their electrophysiological properties, morphology and synaptic input activity remain unknown. One important ionic current described in DMV motoneurons controlling their electrophysiological behaviour is the A-type mediated by voltage-dependent K+ (Kv) channels. Thus, we compared the electrophysiological properties, synaptic activity, morphology, A-type current density, and single cell expression of Kv subunits, that contribute to macroscopic A-type currents, between DMV motoneurons projecting to either the heart or lungs of adult male rats. Using retrograde labelling, we visualized distinct DMV motoneurons projecting to the heart or lungs in acutely prepared medullary slices. Subsequently, whole cell recordings, morphological reconstruction and single motoneuron qRT-PCR studies were performed. DMV pulmonary motoneurons were more depolarized, electrically excitable, presented higher membrane resistance, broader action potentials and received greater excitatory synaptic inputs compared to cardiac DMV motoneurons. These differences were in part due to highly branched dendritic complexity and lower magnitude of A-type K+ currents. By evaluating expression of channels that mediate A-type currents from single motoneurons, we demonstrated a lower level of Kv4.2 in pulmonary versus cardiac motoneurons, whereas Kv4.3 and Kv1.4 levels were similar. Thus, with the distinct electrical, morphological, and molecular properties of DMV cardiac and pulmonary motoneurons, we surmise that these cells offer a new vista of opportunities for genetic manipulation providing improvement of parasympathetic function in cardiorespiratory diseases such heart failure and asthma.

Expression of Truncated Products at the 5'-Terminal Region of RIPK2 and Evolutive Aspects that Support Their Biological Importance.

Alternative splicing is the process of generating different mRNAs from the same primary transcript, which contributes to increase the transcriptome and proteome diversity. Abnormal splicing has been associated with the development of several diseases including cancer. Given that mutations and abnormal levels of the RIPK2 transcript and RIP-2 protein are frequent in tumors, and that RIP-2 modulates immune and inflammatory responses, we investigated alternative splicing events that result in partial deletions of the kinase domain at the N-terminus of RIP-2. We also investigated the structure and expression of the RIPK2 truncated variants and isoforms in different environments. In addition, we searched data throughout Supraprimates evolution that could support the biological importance of RIPK2 alternatively spliced products. We observed that human variants and isoforms were differentially regulated following temperature stress, and that the truncated transcript was more expressed than the long transcript in tumor samples. The inverse was found for the longer protein isoform. The truncated variant was also detected in chimpanzee, gorilla, hare, pika, mouse, rat, and tree shrew. The fact that the same variant has been preserved in mammals with divergence times up to 70 million years raises the hypothesis that it may have a functional significance.

Development, Survival and Reproduction of Nezara viridula (Hemiptera: Pentatomidae) in Sesame Cultivars and Implications for the Management.

Sesame, an oilseed plant with multiple applications, is susceptible to infestations by the stink bug Nezara viridula (Linnaeus, 1758) (Hemiptera: Pentatomidae). This pest suctions the seeds of this plant and injects toxins into them. Possible sources of resistance on sesame cultivars are important to manage this bug. The objective of this study was to evaluate the biological aspects of N. viridula fed on three sesame cultivars aiming to select possible resistance sources for integrated pest management (IPM) programs of this stinkbug. The experimental design used randomized blocks with three treatments and four replications, each with newly emerged N. viridula nymphs fed with sesame capsules of the cultivars BRS Anahí (T1), BRS Morena (T2) and BRS Seda (T3). Two to three green sesame capsules were supplied every two days per group of ten N. viridula nymphs as one replication until the beginning of the adult stage. Adults of this stinkbug were fed in the same manner as its nymphs but with mature sesame capsules until the end of the observations. Survival during each of the five instars and of the nymph stage of N. viridula with green sesame capsules was similar between cultivars, but the duration of the nymph stage was shorter with green capsules of the BRS Morena than with those of the BRS Anahí. The oviposition period, number of egg masses and eggs per female, and the percentage of nymphs hatched were higher with mature capsules of the sesame cultivar BRS Anahí and lower with the others. Nymphs did not hatch from eggs deposited by females fed mature seed capsules of the sesame cultivar BRS Morena, which may indicate a source of resistance against this stinkbug in this cultivar. The worldwide importance of N. viridula to sesame cultivation makes these results useful for breeding programs of this plant aiming to develop genotypes resistant to this bug. In addition, the BRS Morena is a cultivar already commercially available and can be recommended in places where there is a history of incidence of N. viridula, aiming to manage the populations of this pest.

Nitrogen fertilization regulates crosstalk between marandu palisadegrass and Herbaspirillum seropedicae: An investigation based on 15N isotopic analysis and root morphology.

Strategies seeking to increase the use efficiency of nitrogen (N) fertilizers and that benefit plant growth through multiple mechanisms can reduce production costs and contribute to more sustainable agriculture free of polluting residues. Under controlled conditions, we investigated the compatibility between foliar inoculation with an endophytic diazotrophic bacterium (Herbaspirillum seropedicae HRC54) at control and low, medium and high N fertilization levels (0, 25, 50 and 100 mg of N kg-1 as urea, respectively) in Marandu palisadegrass. Common procedures in our research field (biometric and nutritional assessments) were combined with isotopic techniques (natural abundance - δ15N‰ and 15N isotope dilution) and root scanning to determine the contribution of fixed N and recovery of N fertilizer by the grass. Overall, the combined use of 15N isotopic techniques revealed that inoculation not only improved the recovery of applied N-urea from the soil but also provided fixed nitrogen to Marandu palisade grass, resulting in an increase in the total accumulated N. When inoculated plants grew at control and low levels of N, a positive cascade effect encompassing root growth stimulation (nodes of smaller diameter roots), better soil and fertilizer resource exploitation and increased forage production was observed. In contrast, increasing N reduced the contributions of N fixed by H. seropedicae from 21.5% at the control level to 8.6% at the high N level. Given the minimal to no observed growth promotion, this condition was deemed inhibitory to the positive effects of H. seropedicae. We discuss how to make better use of H. seropedicae inoculation in Marandu palisadegrass, albeit on a small scale, thus contributing to a more rational and efficient use of N fertilizers. Finally, we pose questions for future investigations based on 15N isotopic techniques under field conditions, which have great applicability potential.

Artificial neural networks in the modeling of the catalytic activity of a biosensor composed of conjugated polymers and urease.

Thin films of conjugated polymer and enzyme can be used to unravel the interaction between components in a biosensor. Using artificial neural networks (ANNs) improves data interpretability and helps construct models with great capacity for classifying and processing information. The present work used kinetic data from the catalytic activity of urease immobilized in different conjugated polymers to create ANN models using time, substrate concentration, and absorbance as input variables since the models had absorbance in a posterior instant as output value to explore the predictivity of the ANNs. The performance of the models was evaluated by Pearson's correlation coefficient (ρ) and mean squared error (MSE) values. After the learning process, a series of new experiments were performed to verify the generality of the models. As the main results, the best ANN model presented 0.9980 and 3.0736 × 10-5 for ρ and MSE, respectively. For the simulation step, intermediary values of substrate concentration were used. The mean absolute percentage error (MAPE) values were 3.34, 3.07, and 3.78 for 12 mM, 22 mM, and 32 mM concentrations, respectively. Overall, with the simulations, it was possible to ascertain the interpolatory capacity of the model, which has a learning mechanism based on absorbance and time as variables. Thus, the potential of ANNs would be in their use in pre-evaluations, helping to determine the substrate concentration at which there is higher catalytic activity or in determining the linear range of the sensor.

Eicosanoid profiles in an arthritis model: Effects of a soluble epoxide hydrolase inhibitor.

Rheumatoid arthritis is a common systemic inflammatory autoimmune disease characterized by damage to joints, inflammation and pain. It is driven by an increase of inflammatory cytokines and lipids mediators such as prostaglandins. Epoxides of polyunsaturated fatty acids (PUFAs) are lipid chemical mediators in a group of regulatory compounds termed eicosanoids. These epoxy fatty acids (EpFA) have resolutive functions but are rapidly metabolized by the soluble epoxide hydrolase enzyme (sEH) into the corresponding diols. The pharmacological inhibition of sEH stabilizes EpFA from hydrolysis, improving their half-lives and biological effects. These anti-inflammatory EpFA, are analgesic in neuropathic and inflammatory pain conditions. Nonetheless, inhibition of sEH on arthritis and the resulting effects on eicosanoids profiles are little explored despite the physiological importance. In this study, we investigated the effect of sEH inhibition on collagen-induced arthritis (CIA) and its impact on the plasma eicosanoid profile. We measured the eicosanoid metabolites by LC-MS/MS-based lipidomic analysis. The treatment with a sEH inhibitor significantly modulated 11 out of 69 eicosanoids, including increased epoxides 12(13)-EpODE, 12(13)-EpOME, 13-oxo-ODE, 15-HEPE, 20-COOH-LTB4 and decreases several diols 15,6-DiHODE, 12,13-DiHOME, 14,15-DiHETrE, 5,6-DiHETrE and 16,17-DiHDPE. Overall the inhibition of sEH in the rheumatoid arthritis model enhanced epoxides generally considered anti-inflammatory or resolutive mediators and decreased several diols with inflammatory features. These findings support the hypothesis that inhibiting the sEH increases systemic EpFA levels, advancing the understanding of the impact of these lipid mediators as therapeutical targets.

Modulating the sEH/EETs Axis Restrains Specialized Proresolving Mediator Impairment and Regulates T Cell Imbalance in Experimental Periodontitis.

Epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids are short-acting lipids involved in resolution of inflammation. Their short half-life, due to its metabolism by soluble epoxide hydrolase (sEH), limits their effects. Specialized proresolving mediators (SPMs) are endogenous regulatory lipids insufficiently synthesized in uncontrolled and chronic inflammation. Using an experimental periodontitis model, we pharmacologically inhibited sEH, examining its impact on T cell activation and systemic SPM production. In humans, we analyzed sEH in the gingival tissue of periodontitis patients. Mice were treated with sEH inhibitor (sEHi) and/or EETs before ligature placement and treated for 14 d. Bone parameters were assessed by microcomputed tomography and methylene blue staining. Blood plasma metabololipidomics were carried out to quantify SPM levels. We also determined T cell activation by reverse transcription-quantitative PCR and flow cytometry in cervical lymph nodes. Human gingival samples were collected to analyze sEH using ELISA and electrophoresis. Data reveal that pharmacological sEHi abrogated bone resorption and preserved bone architecture. Metabololipidomics revealed that sEHi enhances lipoxin A4, lipoxin B4, resolvin E2, and resolvin D6. An increased percentage of regulatory T cells over Th17 was noted in sEHi-treated mice. Lastly, inflamed human gingival tissues presented higher levels and expression of sEH than did healthy gingivae, being positively correlated with periodontitis severity. Our findings indicate that sEHi preserves bone architecture and stimulates SPM production, associated with regulatory actions on T cells favoring resolution of inflammation. Because sEH is enhanced in human gingivae from patients with periodontitis and connected with disease severity, inhibition may prove to be an attractive target for managing osteolytic inflammatory diseases.

Soluble epoxide hydrolase inhibitors for smoking-associated inflammatory lung diseases and chronic obstructive pulmonary disease: a meta-analytical systematic review of preclinical and clinical studies.

An evaluation of the inflammatory enzymatic interactions related to pulmonary function can help identify biomarkers for interventions or prophylactic measures to improve patient prognosis. This study aimed to determine the effect of epoxide hydrolase inhibition by GSK2256294 in different pulmonary inflammation models. A secondary search was performed using Medline/PubMed, Web of Science, SciELO, Cochrane Library, Embase, Academic Google, and gray literature by two independent reviewers, who analyzed the methodological quality and consistency of the data. Different variables were compared using a meta-analysis. A total of 86 studies were found, 4 of which were selected from the gray literature. Based on the eligibility criteria, two clinical and one preclinical studies were evaluated. GSK2256294 inhibited the soluble epoxide hydrolase enzyme in both clinical and preclinical models, exhibiting greater effectiveness in clinical studies and contributing to the anti-inflammatory activity mediated by the eicosatrienoic pathway by reducing the levels of dihydroxyeicosatrienoic acids and leukotoxin-diol. Overall, GSK2256294 was identified as a promising drug for controlling the deleterious manifestations of lung inflammation. Further clinical and preclinical studies are required to ensure consistency among the evidence and identify other biological activities mediated by GSK2256294.