Response of Fusarium oxysporum soil isolate to amphotericin B and fluconazole at the proteomic level.

Fusarium oxysporum is a cross-kingdom pathogen that infects humans, animals, and plants. The primary concern regarding this genus revolves around its resistance profile to multiple classes of antifungals, particularly azoles. However, the resistance mechanism employed by Fusarium spp. is not fully understood, thus necessitating further studies to enhance our understanding and to guide future research towards identifying new drug targets. Here, we employed an untargeted proteomic approach to assess the differentially expressed proteins in a soil isolate of Fusarium oxysporum URM7401 cultivated in the presence of amphotericin B and fluconazole. In response to antifungals, URM7401 activated diverse interconnected pathways, such as proteins involved in oxidative stress response, proteolysis, and lipid metabolism. Efflux proteins, antioxidative enzymes and M35 metallopeptidase were highly expressed under amphotericin B exposure. Antioxidant proteins acting on toxic lipids, along with proteins involved in lipid metabolism, were expressed during fluconazole exposure. In summary, this work describes the protein profile of a resistant Fusarium oxysporum soil isolate exposed to medical antifungals, paving the way for further targeted research and discovering new drug targets.

Abscisic acid-mediated guard cell metabolism regulation.

Abscisic acid (ABA) is crucial for plant water deficit (WD) acclimation, but how the interplay between ABA and guard cell (GC) metabolism aids plant WD acclimation remains unclear. Here, we investigated how ABA regulates GC metabolism and how this contributes to plant WD acclimation using tomato wild type (WT) and the ABA-deficient sitiens mutant. These genotypes were characterized at physiological, metabolic, and transcriptional levels under recurring WD periods and were used to perform a13C-glucose labelling experiment using isolated guard cells following exogenously applied ABA. ABA deficiency altered the level of sugars and organic acids in GCs in both irrigated and WD plants and the dynamic of accumulation/degradation of these compounds in GCs during the dark-to-light transition. WD-induced metabolic changes were more pronounced in sitiens than WT GCs. Results from the 13C-labelling experiment indicate that ABA is required for the glycolytic fluxes toward malate and acts as a negative regulator of a putative sucrose substrate cycle. The expression of key ABA-biosynthetic genes was higher in WT than in sitiens GCs after two cycles of WD. Additionally, the intrinsic leaf water use efficiency increased only in WT after the second WD cycle, compared to sitiens. Our results highlight that ABA deficiency disrupts the homeostasis of GC primary metabolism and the WD memory, negatively affecting plant WD acclimation. Our study demonstrates which metabolic pathways are activated by WD and/or regulated by ABA in GCs, which improves our understanding of plant WD acclimation, with clear consequences for plant metabolic engineering in the future.

Secondary production of Acartia tonsa Dana, 1849 and A. lilljeborgii Giesbrecht, 1889 in an Amazonian estuary (Brazil).

The dynamics of the copepods A. tonsa and A. lilljeborgii were described for the first time in the Taperaçu Estuary. The acartiids were collected using plankton nets (200 µm) in June 2012, March 2013 (rainy season) and September 2012 and 2013 (dry season). The oscillations in rainfall and the fluctuations in hydrological variables influenced the abundance, biomass, and production of both A. tonsa (17 ± 23 to 8501 ± 13,248 ind.m-3; 16,385.29 mg.C.m-3; 0.09 ± 0.21 to 355.17 ± 590.84 mg.C.m-3.d-1) and A. lilljeborgii (14 ± 11 to 1470 ± 1591 ind.m-3; 22,398.40 mg.C.m-3; 177.99 ± 263.13 mg.C.m-3.d-1) with clear monthly, seasonal, and spatial patterns. The high levels of production observed may be related to the presence of waters rich in particulate organic material derived from the adjacent mangrove forests. This material is consumed by a number of copepod species, in particular A. tonsa and A. lilljeborgii, favoring the development and reproduction of both species which are characterized by high rates of productivity in the study estuary. The present results indicate that the biomass and productivity in equatorial mangrove estuaries may be relatively high in comparison with the levels observed in other coastal systems around the world and that earlier stages of both species have a great relevance for biomass and production in Amazonian estuaries.

[UhpTE350Q mutation along with the presence of fosA6/5 genes in the genome probably contributes to inherent fosfomycin resistance of Klebsiella pneumoniae].

OBJECTIVE: To investigate the molecular mechanism underlying inherent fosfomycin resistance of Klebsiella pneumoniae (K. pneumoniae). METHODS: The draft genomic sequences of 14 clinical hypervirulent/hypermucoviscous K. pneumoniae (HvKP/ HmKP) isolates were obtained using the next-generation sequencing technology. The genomic sequences were analyzed using the Resistance Gene Identifier (RGI) software for predicting the resistome based on homology and SNP models in the Comprehensive Antibiotic Resistance Database (CARD) and for identification of the presence of phosphomycin resistancerelated genes uhpt and fosA and their mutations in the bacterial genomes. The results were verified by analyzing a total of 521 full-length genomic sequences of K. pneumonia strains obtained from GenBank. RESULTS: All the 14 clinical isolates of HvKP/ HmKP carried hexose phosphate transporter (UhpT) gene mutation, in which the glutamic acid was mutated to glutamine at 350aa (UhpTE350Q mutation); the presence of fosA6 gene was detected in 12 (85.71%) of the isolates and fosA5 gene was detected in the other 2 (14.29%) isolates. Analysis of the genomic sequences of 521 K. pneumonia strains from GenBank showed that 508 (97.50%) strains carried UhpTE350Q mutation, 439 (84.26%) strains harbored fosA6, and 80 (15.36%) strains harbored fosA5; 507 (97.31%) strains were found to have both UhpTE350Q mutation and fosA6/5 genes in the genome. Only 12 (2.30%) strains carried fosA6/5 genes without UhpTE350Q mutation; 1 (0.19%) strain had only UhpTE350Q mutation without fosA6/5 genes, and another strain contained neither UhpTE350Q mutation nor fosA6/5 genes. CONCLUSION: UhpTE350Q mutation with the presence of fosA6/5 genes are ubiquitous in K. pneumonia genomes, indicating a possible intrinsic mechanism of fosfomycin resistance in the bacterium to limit the use of fosfomycin against infections caused by K. pneumoniae, especially the multi-resistant HvKP/HmKP strains.

Comparison between p-distance and single-locus species delimitation models for delineating reproductively tested strains of pennate diatoms (Bacillariophyceae) using cox1, rbcL and ITS.

Several automated molecular methods have emerged for distinguishing eukaryote species based on DNA sequence data. However, there are knowledge gaps around which of these single-locus methods is more accurate for the identification of microalgal species, such as the highly diverse and ecologically relevant diatoms. We applied genetic divergence, Automatic Barcode Gap Discovery for primary species delimitation (ABGD), Assemble Species by Automatic Partitioning (ASAP), Statistical Parsimony Network Analysis (SPNA), Generalized Mixed Yule Coalescent (GMYC) and Poisson Tree Processes (PTP) using partial cox1, rbcL, 5.8S + ITS2, ITS1 + 5.8S + ITS2 markers to delineate species and compare to published polyphasic identification data (morphological features, phylogeny and sexual reproductive isolation) to test the resolution of these methods. ASAP, ABGD, SPNA and PTP models resolved species of Eunotia, Seminavis, Nitzschia, Sellaphora and Pseudo-nitzschia corresponding to previous polyphasic identification, including reproductive isolation studies. In most cases, these models identified diatom species in similar ways, regardless of sequence fragment length. GMYC model presented smallest number of results that agreed with previous published identification. Following the recommendations for proper use of each model presented in the present study, these models can be useful tools to identify cryptic or closely related species of diatoms, even when the datasets have relatively few sequences.

Application of 1H HR-MAS NMR-Based Metabolite Fingerprinting of Marine Microalgae.

Natural products from the marine environment as well as microalgae, have been known for the complexity of the metabolites they produce due to their adaptability to different environmental conditions, which has been an inexhaustible source of several bioactive properties, such as antioxidant, anti-tumor, and antimicrobial. This study aims to characterize the main metabolites of three species of microalgae (Nannochloropsis oceanica, Chaetoceros muelleri, and Conticribra weissflogii), which have important applications in the biofuel and nutrition industries, by 1H High-resolution magic angle spinning nuclear magnetic resonance (1H HR-MAS NMR), a method which is non-destructive, is highly reproducible, and requires minimal sample preparation. Even though the three species were found in the same ecosystem and a superior production of lipid compounds was observed, important differences were identified in relation to the production of specialized metabolites. These distinct properties favor the use of these compounds as leaders in the development of new bioactive compounds, especially against environmental, human, and animal pathogens (One Health), and demonstrate their potential in the development of alternatives for aquaculture.

A study about management of drugs for leprosy patients under medical monitoring: A solution based on AHP-Electre decision-making methods.

Leprosy, also known as Hansen's, is one of the listed neglected tropical diseases as a major health problem global. Treatment is one of the main alternatives, however, the scarcity of medication and its poor distribution are important factors that have driven the spread of the disease, leading to irreversible and multi-resistant complications. This paper uses a distribution methodology to optimize medication administration, taking into account the most relevant attributes for the epidemiological profile of patients and the deficit in treatment via Polychemotherapy. Multi-criteria Decision Methods were applied based on AHP-Electre model in a database with information from patients in the state of Para between 2015 and 2020. The results pointed out that 84% of individuals did not receive any treatment and, among these, the method obtained a gain in the distribution of 68% in patients with positive diagnosis for leprosy.

Update on artificial insemination: Semen, techniques, and sow fertility.

Over the years, reproductive efficiency in the swine industry has focused on reducing the sperm cell number required per sow. Recent advances have included the identification of subfertile boars, new studies in extended semen quality control, new catheters and cannulas for intrauterine artificial insemination (AI), and fixed-time AI under commercial use. Therefore, it is essential to link field demands with scientific studies. In this review, we intend to discuss the current status of porcine AI, pointing out challenges and opportunities to improve reproductive efficiency.

Identification of Potential New Aedes aegypti Juvenile Hormone Inhibitors from N-Acyl Piperidine Derivatives: A Bioinformatics Approach.

Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA -265.95 ± 1.32 kJ/mol and -124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = -216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= -435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.

Whole-Body MRI in Limb Girdle Muscular Dystrophy Type R1/2A: Correlation With Clinical Scores.

INTRODUCTION/AIM: The most common limb girdle muscular dystrophy (LGMD) worldwide is LGMD type R1 (LGMDR1). The aim of this study was to correlate the MRI findings with functional scores and to describe the whole-body MRI (WBMRI) pattern in a LGMDR1 Brazilian cohort. METHODS: LGMDR1 patients under follow-up in three centers were referred for the study. Clinical data were collected and a functional evaluation was performed, consisting of Gardner-Medwin and Walton (GMW) and Brooke scales. All patients underwent a WBMRI study (1.5T) with axial T1 and STIR images. Fifty-one muscles were semiquantitatively assessed regarding fatty infiltration and muscle edema. RESULTS: The study group consisted of 18 patients. The highest fatty infiltration scores involved the serratus anterior, biceps femoris long head, adductor magnus, and lumbar erector spinae. There was a latero-medial and caudo-cranial descending gradient of involvement of the paravertebral muscles, with erector spinae being significantly more affected than the transversospinalis muscles (p < 0.05). A striped appearance that has been dubbed the "pseudocollagen sign" was present in 72% of the patients. There was a positive correlation between the MRI score and GMW (Rho:0.83) and Brooke (Rho:0.53) scores. DISCUSSION: WBMRI in LGMDR1 allows a global patient evaluation including involvement of the paraspinal muscles, usually an underestimated feature in the clinical and imaging study of myopathies. Knowledge of the WBMRI pattern of LGMDR1 involvement can be useful in the diagnostic approach and in future studies to identify the best target muscles to serve as outcome measures in clinical trials.

Correlation Between Implant Positioning and Functional Outcomes in Partial Shoulder Resurfacing.

Objective The present study aimed to correlate functional outcomes and implant positioning in a case series of partial shoulder resurfacing arthroplasties. Methods A total of 25 patients were assessed for range of motion, functional outcome per the University of California at Los Angeles (UCLA) score and radiographic findings. Pre- and postoperative data were compared. In addition, patients were grouped according to the cervical-diaphyseal angle (CDA) determined by an anteroposterior radiography and to the retroversion angle (RVA) determined by an axillary radiography. A CDA from 130° to 140° and a RVA from 20° to 40° consisted in ideal positioning (anatomical standard). Data were analyzed using the Wilcoxon signed-rank test, analysis of variance (ANOVA) followed by the Kruskal-Wallis test or the Mann-Whitney test as appropriate. Results The mean follow-up time was 48.3 months (12 to 67 months). The postoperative functional score (31.5) was higher than the preoperative score (15.5) ( p < 0.001). In 6 patients, the implant was in anatomical positioning, while implant positioning was considered "nonstandard" in 19 subjects. Seven patients had a CDA < 130°, and 14 patients had a CDA ranging from 130° to 140°; in addition, the CDA was > 140° in 4 subjects. The RVA was up to 20° in 15 patients and ranged from 20° to 40° in 10 subjects. Using these criteria to group patients, the postoperative clinical-functional parameters were not statistically different from the preoperative findings ( p > 0.05). Conclusion Partial shoulder resurfacing results in significant postoperative functional recovery in patients with degenerative joint diseases. However, implant positioning assessed by CDA and RVA does not correlate with clinical-functional outcomes and, therefore, it is an inaccurate indicator of surgical success. Level of Evidence IV; Case Series.

Brazilian Food Handlers' Years of Work in the Foodservice and Excess Weight: A Nationwide Cross-Sectional Study.

This study aimed to evaluate the association between the years of work of food handlers in the foodservice and excess weight among Brazilian low-income food handlers. A total of 559 food handlers from all Brazilian regions were characterized using a questionnaire. Weight and height were measured to estimate the Body Mass Index and classify the individuals. The association between food handlers' years of work in the foodservice, anthropometric status, and other variables (gender, age group, educational level, participation in a government program and per capita income at home and energetic consumption) were performed using Pearson's chi-square test (p < 0.05). Multinomial logistic regression analyses were performed (p < 0.05) as well as sensitivity tests using the outcome continuously and transformed, excluding underweight individuals, in a multivariate linear regression model. Most of the sample was female (63.1%), aged between 21 and 40 years old (63.5%), and 53.3% had studied up to complete elementary school. Almost 41% of the food handlers had less than half the minimum wage per capita income. Of the evaluated individuals, 59.9% presented excess weight. There was an association with family per capita income (Odds Ratio - OR: 1.73; Confidence interval - CI95%: 1.09-2.75); handlers whose per capita income was ≤0.5 minimum wage had a 73% higher chance of obesity than those with higher income. Working in foodservive ≥3 years increased the chance of being overweight by 96% compared to those who work for <3 years (OR: 1.96; CI95%: 1.11-3.49). No significant association was found between the years of work of food handlers in the foodservice and obesity. Since work-related factors may contribute to the high prevalence of excess weight, including working in a food handling environment, the government and employers should consider workplace interventions. These would guide the food handlers in avoiding high rates of excess weight and their consequences on public health. Excess weight is an important driver of costs in the workplace associated with absenteeism, job change, and diseases. More studies are necessary to clarify the relationship between the factors related to work and the anthropometric status of food handlers since excess weight is multifactorial.

Correlation Between Implant Positioning and Functional Outcomes in Partial Shoulder Resurfacing / Correlação entre posicionamento do implante das artroplastias parciais de recobrimento do ombro e os resultados funcionais

Abstract Objective The present study aimed to correlate functional outcomes and implant positioning in a case series of partial shoulder resurfacing arthroplasties. Methods A total of 25 patients were assessed for range of motion, functional outcome per the University of California at Los Angeles (UCLA) score and radiographic findings. Preand postoperative data were compared. In addition, patients were grouped according to the cervical-diaphyseal angle (CDA) determined by an anteroposterior radiography and to the retroversion angle (RVA) determined by an axillary radiography. A CDA from 130° to 140° and a RVA from 20° to 40° consisted in ideal positioning (anatomical standard). Data were analyzed using the Wilcoxon signed-rank test, analysis of variance (ANOVA) followed by the Kruskal-Wallis test or the Mann-Whitney test as appropriate. Results The mean follow-up time was 48.3 months (12 to 67 months). The postoperative functional score (31.5) was higher than the preoperative score (15.5) (p < 0.001). In 6 patients, the implant was in anatomical positioning, while implant positioning was considered "nonstandard" in 19 subjects. Seven patients had a CDA < 130°, and 14 patients had a CDA ranging from 130° to 140°; in addition, the CDA was > 140° in 4 subjects. The RVA was up to 20° in 15 patients and ranged from 20° to 40° in 10 subjects. Using these criteria to group patients, the postoperative clinical-functional parameters were not statistically different from the preoperative findings (p > 0.05). Conclusion Partial shoulder resurfacing results in significant postoperative functional recovery in patients with degenerative joint diseases. However, implant positioning assessed by CDA and RVA does not correlate with clinical-functional outcomes and, therefore, it is an inaccurate indicator of surgical success. Level of Evidence IV; Case Series.

Resumo Objetivo O objetivo do presente estudo é correlacionar os resultados funcionais de uma série de casos de artroplastias parciais de recobrimento do ombro com o posicionamento do implante. Métodos Um total de 25 pacientes foram avaliados em relação à amplitude de movimentos, à avaliação funcional pelo escore de Universidade da Califórnia Los Angeles (UCLA) e por análise radiográfica. Os dados pré- e pós-operatórios foram comparados. Adicionalmente, os pacientes foram agrupados quanto ao ângulo cérvico-diafisário (ACD) avaliado na radiografia em anteroposterior e quanto ao ângulo de retroversão (ARV) avaliado na radiografia em posição axilar. Foi considerado como posicionamento ideal (padrão anatômico) um ACD entre 130° e 140° e um ARV entre 20° e 40°. Os dados foram analisados pelo teste pareado de Wilcoxon, pela análise de variância (ANOVA, na sigla em inglês) seguida pelo pós-teste de Kruskal-Wallis ou pelo teste de Mann-Whitney, quando apropriado. Resultados O seguimento médio foi de 48,3 meses (12 a 67 meses). A avaliação funcional pós-operatória (31,5) foi melhor do que a pré-operatória (15,5) (p < 0,001). Seis pacientes apresentaram posicionamento anatômico do implante, enquanto 19 pacientes foram considerados "fora do padrão." Sete pacientes apresentaram um ACD < 130°, quatorze apresentaram um ACD entre 130° e 140°, e quatro apresentaram um ACD >140°. Quinze pacientes apresentaram um ARV ≤ 20°, e 10 entre 20° e 40°. Utilizando esses critérios para agrupar os pacientes, a comparação dos parâmetros da avaliação clínico-funcional pós-operatória não foi estatisticamente diferente (p > 0,05). Conclusão A artroplastia parcial de recobrimento do ombro oferece significativa recuperação funcional pós-operatória em pacientes com doenças degenerativas articulares. Entretanto, o posicionamento do implante avaliado pelos ACD e ARV não se correlaciona com o resultado clínico-funcional, sendo, portanto, uma medida imprecisa de sucesso da cirurgia. Nível de Evidência IV, Série de Casos.

Chemical Profile and Antimicrobial Activity of the Marine Diatom Chaetoceros muelleri.

Microalgae, due to its rapid growth, low nutritional requirements, and versatility of adaptation to different environmental conditions, has aroused the biotechnological interest, synthesizing novel molecules with antioxidant, anticoagulant, anti-inflammatory, antitumor, and antimicrobial activities. In this sense, we carried out the bioprospection of Chaetoceros muelleri, a marine diatom employed in aquaculture, as a candidate to the development of new drugs for the treatment of bacterial infections. The chemical profile of extracts in different solvents (hexane, chloroform, methylene chloride, ethyl acetate, methanol, and acetone) were analyzed by 1 H-NMR. The hexane extract was the most active against all bacteria species tested, including Mycobacterium tuberculosis, with a minimum inhibitory concentration of 100 µg/ml. Contrarily, the methanol extract was inactive against all tested microorganisms and, in addition, was the only one with IC50 >800 µg/mL, showing no cytotoxicity in VERO cell lines. All other extracts showed antibacterial potential and IC50 values varying between 267.58 and 142.47 µg/ml. The fact that C. muelleri is a microalga easily grown on bioreactors on a large scale may promote its biotechnological use, especially as scaffolds for the development of new compounds against bacterial species of clinical and public health interest.

Multivariate optimization results in an edible extract from Ilex paraguariensis unexplored residues with a high amount of phenolic compounds.

Ilex paraguariensis A. St. Hil. plants are used for the preparation of food and drinks which are widely consumed worldwide. During the harvest season of these plants, 2-5 ton hec-1 of agricultural residue is generated, which remains underutilized. Therefore, this study aimed to obtain an edible extract with high content of bioactive compounds and antimicrobial properties from the agricultural residue of I. paraguariensis for industrial use in food applications. The extraction conditions were optimized through a multivariate experimental design using ethanol:water. The extracted compounds were characterized by HPLC-ESY-QTOF-MS. In the optimal extraction conditions, 55 compounds were extracted, including 8 compounds that were not previously reported in I. paraguariensis. The method proved to be simple, fast, economical and environmentally friendly, with the use of green solvents. This optimization allowed for the extraction of 15.07 g of phenolic compounds per 100 g of residue. The extract showed high antioxidant activity and the capacity to inhibit Staphylococcus aureus. Results indicate that it is possible to obtain an edible extract with a high content of bioactive compounds, particularly phenolic compounds, from the I. paraguariensis residue, which has high prospects for the valorization of unexplored natural resources.

Acetylcholinesterase inhibitory activity of Ocotea pomaderroides extracts: HPLC-MS/MS characterization and molecular modeling studies.

The present work describes the acetylcholinesterase inhibitory activity of Ocotea pomaderroides extracts besides the chemical composition of chromatographic fractions. The hexane, dichloromethane and ethyl acetate extract soluble fractions showed high Electrophorus electricus acetylcholinesterase (EelAChE) inhibition (92.18, 71.86 and 74.25%, respectively) while the butanolic and aqueous extracts showed moderate to low activities (44.48 and 20.74%, respectively). The high-performance liquid chromatography coupled with electrospray ionization multiple-stage mass spectrometry (HPLC-ESI-MSn) analysis led to the identification of the alkaloids and flavonol glycoside derivatives present in these extracts. The binding profile of the alkaloids and their atomic effect on 3D structure of Electrophorus electricus AchE (EelAChE) were assessed with molecular modeling.

Accelerated apoptosis, oxidative stress, and cholinergic inflammation in blood of metalworkers.

Metalworkers are exposed to numerous chemicals in their workplace environment, such as solvents, heavy metals, and metalworking fluids, that have a negative impact on their health. Furthermore, there is an increase in the prevalence of chronic diseases among metalworkers; however, the molecular mechanisms involved in this increased predisposition to chronic diseases are unclear. Considering that occupational exposure represents a potential risk for metalworkers, the aim of this study was to measure biomarkers of oxidative stress, inflammation, and cytotoxicity in the peripheral blood of metalworkers from Southern Brazil. The study included 40 metalworkers and 20 individuals who did not perform activities with any recognized exposure to chemical substances, such as those working in administration, commerce, and education, as controls. Cellular and molecular biomarkers as leukocyte viability, intracellular production of reactive species, mitochondrial mass and membrane potential and plasma lipid peroxidation, sulfhydryl groups, total antioxidant capacity, and butyrylcholinesterase activity were evaluated in the blood of metalworkers and controls. Metalworkers were found to have higher rates of apoptosis, increased production of reactive species, and increased mitochondrial potential and mass in leukocytes associated with decreased antioxidant defenses and increased activity of the butyrylcholinesterase enzyme in their plasma. It can be concluded that cytotoxicity, oxidative stress, and inflammation are involved in the multiplicity of health outcomes related to chemical exposure in the metalworking industry.

Hydroxycinnamic acid-spermidine amides from Tetragonisca angustula honey as anti-Neospora caninum: In vitro and in silico studies.

Tetragonisca angustula honey was fractioned in a SiO2 column to furnish three fractions (A-C) in which four hydroxycinnamic acid-Spermidine amides (HCAAs), known as N', N″, N‴-tris-p-coumaroyl spermidine, N', N″-dicaffeoyl, N‴-coumaroyl spermidine, N', N″, N‴-tris-caffeoyl spermidine and N', N″-dicaffeoyl and N‴-feruloyl spermidine were identified in the fractions B and C by electrospray ionization tandem mass spectrometry. A primary culture model previously infected with Neospora caninum (72 h) was used to evaluate the honey fractions (A-C) for two-time intervals: 24 and 72 h. Parasitic reduction ranged from 38% on fraction C (12.5 µg/ml), after 24 h, to 54% and 41% with fractions B and C (25 µg/ml) after 72 h of treatment, respectively. Additionally, HCAAs did not show any cell toxicity for 24 and 72 h. For infected cultures (72 h), the active fractions B (12.5 µg/ml) and C (25 µg/ml) decreased their NO content. In silico studies suggest that HCAAs may affect the parasite's redox pathway and improve the oxidative effect of NO released from infected cells. Here, we presented for the first time, that HCAAs from T. angustula honey have the potential to inhibit the growth of N. caninum protozoa.