Luminescent Supramolecular Metallogels: Drug Loading and Eu(III) as Structural Probe.

Supramolecular metallogels combine the rheological properties of gels with the color, magnetism, and other properties of metal ions. Lanthanide ions such as Eu(III) can be valuable components of metallogels due to their fascinating luminescence. In this work, we combine Eu(III) and iminodiacetic acid (IDA) into luminescent hydrogels. We investigate the tailoring of the rheological properties of these gels by changes in their metal:ligand ratio. Further, we use the highly sensitive Eu(III) luminescence to obtain information about the chemical structure of the materials. In special, we take advantage of computational calculations to employ an indirect method for structural elucidation, in which the simulated luminescent properties of candidate structures are matched to the experimental data. With this strategy, we can propose molecular structures for different EuIDA gels. We also explore the usage of these gels for the loading of bioactive molecules such as OXA, observing that its aldose reductase activity remains present in the gel. We envision that the findings from this work could inspire the development of luminescent hydrogels with tunable rheology for applications such as 3D printing and imaging-guided drug delivery platforms. Finally, Eu(III) emission-based structural elucidation could be a powerful tool in the characterization of advanced materials.

Systemic Sirtuin 1 as a Potential Target to Mediate Interactions Between Body Fat and Testosterone Concentration in Master Athletes.

Evidence indicates that master athletes have higher concentration of Sirtuin 1 (Sirt1), lower body fat (BF), and greater activity of the hypothalamic-pituitary-gonadal axis in comparison to untrained peers. However, no published data have demonstrated possible mediation effect of Sirt1 in the interaction of BF and testosterone in this population. Therefore, this study compared and verified possible associations between Sirt1, BF, fat mass index (FMI), testosterone, luteinizing hormone (LH), and testosterone/luteinizing hormone (T/LH) ratio in middle-aged master athletes (n = 54; 51.22 ± 7.76 years) and control middle-aged peers (n = 21; 47.76 ± 8.47 years). Venous blood was collected for testosterone, LH, and Sirt1. BF was assessed through skinfold protocol. Although LH concentration did not differ between groups, master athletes presented higher concentration of Sirt1, testosterone, and T/LH ratio, and lower BF and FMI in relation to age-matched nonathletes. Moreover, Sirt1 correlated positively with testosterone and T/LH ratio, negatively with BF, and was not significantly correlated with LH (mediation analysis revealed the effect of BF on testosterone is mediated by Sirt1 and vice versa; R2 = .1776; p = .032). In conclusion, master athletes have higher testosterone, T/LH ratio, and Sirt1, and lower BF and FMI in relation to untrained peers. Furthermore, Sirt1 was negatively associated with BF and positively associated with testosterone and T/LH ratio. These findings suggest that increased circulating Sirt1, possibly due to the master athlete's training regimens and lifestyle, exhibits a potential mediation effect on the interaction between endocrine function and body composition.

Crucial role of carbon monoxide as a regulator of diarrhea caused by cholera toxin: Evidence of direct interaction with toxin.

The present study evaluated the role of heme oxygenase 1 (HO-1)/carbon monoxide (CO) pathway in the cholera toxin-induced diarrhea and its possible action mechanism. The pharmacological modulation with CORM-2 (a CO donor) or Hemin (a HO-1 inducer) decreased the intestinal fluid secretion and Cl- efflux, altered by cholera toxin. In contrast, ZnPP (a HO-1 inhibitor) reversed the antisecretory effect of Hemin and potentiated cholera toxin-induced intestinal secretion. Moreover, CORM-2 also prevented the alteration of intestinal epithelial architecture and local vascular permeability promoted by cholera toxin. The intestinal absorption was not altered by any of the pharmacological modulators. Cholera toxin inoculation also increased HO-1 immunoreactivity and bilirubin levels, a possible protective physiological response. Finally, using fluorometric technique, ELISA assay and molecular docking simulations, we show evidence that CO directly interacts with cholera toxin, forming a complex that affects its binding to GM1 receptor, which help explain the antisecretory effect. Thus, CO is an essential molecule for protection against choleric diarrhea and suggests its use as a possible therapeutic tool.

Relationship of Testosterone, LH, Estradiol, IGF-1, and SHBG with Physical Performance of Master Athletes.

Purpose: The aim of this study was to investigate and compare the levels of luteinizing hormone (LH), testosterone (T), estradiol (ES), sex hormone-binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1) in master sprint (MS) and master endurance (ME) athletes. Additionally, the possible associations between these hormones, body composition, and lipid profile with athletic performance (% of performance in relation to the current world record) were analyzed. Materials and Methods: The participants were all men: (i) 34 MS (51.0 ± 6.8 years); and (ii) 32 ME (51.7 ± 9.4 years). Student's t-tests for independent samples were performed to compare all variables between groups. Results: MS had a significantly higher (p = .008) average IGF-1 (154.78 ± 29.85 ng/mL) when compared to ME (129.92 ± 25.48 ng/mL). Performance was significantly correlated with IGF-1 (r = 0.424). The MS group had a moderately lower body fat than ME athletes (MS 12.54 ± 4.07 vs. ME 14.60 ± 4.12; p = .078; d = 0.503). Conclusions: Thus, strength/power training exercise/sport seems to be more beneficial for obtaining a higher IGF-1 compared to aerobic/distance exercise/sport. In addition, LH, T, ES, and SHBG were similar between the two groups of athletes and were comparable to the reference values of younger adults.

Pharmacological assessment of the antineoplastic and immunomodulatory properties of a new spiroindolone derivative (7',8'-Dimethoxy-1',3'-dimethyl-1,2,3',4'-tetrahydrospiro[indole-3,5'-pyrazolo[3,4-c]isoquinolin]-2-one) in chronic myeloid leukemia.

The discovery and development of effective novel compounds is paramount in oncology for improving cancer therapy. In this study, we developed a new derivative of spiroindolone (7',8'-Dimethoxy-1',3'-dimethyl-1,2,3',4'-tetrahydrospiro[indole-3,5'- pyrazolo[3,4-c]isoquinolin]-2-one) and evaluated its anticancer- and immunomodulatory potential in a vitro model of chronic leukemia. We utilized the chronic leukemia cell line K562, as well as non-cancerous peripheral blood mononuclear cells (PBMC) and Vero cells (kidney epithelium of Cercopithecus aethiops). We assessed the cytotoxicity of the compound using the MTT assay, and performed cell cycle assays to determine its impact on different stages of the cell cycle. To evaluate its antineoplastic activity, we conducted a colony formation test to measure the effect of the compound on the clonal growth of cancer cells. Furthermore, we evaluated the immunomodulatory activity of the compound by measuring the levels of pro and anti-inflammatory cytokines. The study findings demonstrate that the spiroindolone-derived compound exerted noteworthy cytotoxic effects against K562 cells, with an IC50 value of 25.27 µg/mL. Additionally, it was observed that the compound inhibited the clonal proliferation of K562 cells while displaying minimal toxicity to normal cells. The compound exhibited its antiproliferative activity by inducing G2/M cell cycle arrest, preventing the entry of K562 cells into mitosis. Notably, the compound demonstrated an immunomodulatory effect by upregulating the production of cytokines IL-6 and IL-12/23p40. In conclusion, the spiroindolone-derived compound evaluated in this study has demonstrated significant potential as a therapeutic agent for the treatment of chronic myeloid leukemia. Further investigations are warranted to explore its clinical applications.

Inhibition of 3-Hydroxykynurenine Transaminase from Aedes aegypti and Anopheles gambiae: A Mosquito-Specific Target to Combat the Transmission of Arboviruses.

Arboviral infections such as Zika, chikungunya, dengue, and yellow fever pose significant health problems globally. The population at risk is expanding with the geographical distribution of the main transmission vector of these viruses, the Aedes aegypti mosquito. The global spreading of this mosquito is driven by human migration, urbanization, climate change, and the ecological plasticity of the species. Currently, there are no specific treatments for Aedes-borne infections. One strategy to combat different mosquito-borne arboviruses is to design molecules that can specifically inhibit a critical host protein. We obtained the crystal structure of 3-hydroxykynurenine transaminase (AeHKT) from A. aegypti, an essential detoxification enzyme of the tryptophan metabolism pathway. Since AeHKT is found exclusively in mosquitoes, it provides the ideal molecular target for the development of inhibitors. Therefore, we determined and compared the free binding energy of the inhibitors 4-(2-aminophenyl)-4-oxobutyric acid (4OB) and sodium 4-(3-phenyl-1,2,4-oxadiazol-5-yl)butanoate (OXA) to AeHKT and AgHKT from Anopheles gambiae, the only crystal structure of this enzyme previously known. The cocrystallized inhibitor 4OB binds to AgHKT with K i of 300 µM. We showed that OXA binds to both AeHKT and AgHKT enzymes with binding energies 2-fold more favorable than the crystallographic inhibitor 4OB and displayed a 2-fold greater residence time τ upon binding to AeHKT than 4OB. These findings indicate that the 1,2,4-oxadiazole derivatives are inhibitors of the HKT enzyme not only from A. aegypti but also from A. gambiae.

Intensity of Depression Symptoms Is Negatively Associated with Catalase Activity in Master Athletes.

BACKGROUND: This study examined associations between scores of depression (DEPs), thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), and catalase activity (CAT) in master athletes and untrained controls. METHODS: Participants were master sprinters (MS, n = 24; 50.31 ± 6.34 year), endurance runners (ER, n = 11; 51.35 ± 9.12 year), untrained middle-aged (CO, n = 13; 47.21 ± 8.61 year), and young untrained (YU, n = 15; 23.70 ± 4.02 year). CAT, SOD, and TBARS were measured in plasma using commercial kits. DEPs were measured by the Beck Depression Inventory-II. An ANOVA, Kruskal-Wallis, Pearson's, and Spearman's correlations were applied, with a significance level of p ≤ 0.05. RESULTS: The CATs of MS and YU [760.4 U·µL 1 ± 170.1 U·µL 1 and 729.9 U·µL 1 ± 186.9 U·µL 1] were higher than CO and ER. The SOD levels in the YU and ER [84.20 U·mL-1 ± 8.52 U·mL-1 and 78.24 U·mL-1 ± 6.59 U·mL-1 (p < 0.0001)] were higher than CO and MS. The TBARS in CO [11.97 nmol·L-1 ± 2.35 nmol·L-1 (p < 0.0001)] was higher than in YU, MS and ER. MS had lower DEPs compared to the YU [3.60 ± 3.66 vs. 12.27 ± 9.27 (p = 0.0002)]. A negative correlation was found between CAT and DEPs for master athletes [r = -0.3921 (p = 0.0240)] and a weak correlation [r = -0.3694 (p = 0.0344)] was found between DEPs and the CAT/TBARS ratio. CONCLUSIONS: In conclusion, the training model of master sprinters may be an effective strategy for increasing CAT and reducing DEPs.

Phytochemical characterization of oil and protein fractions isolated from Japanese quince (Chaenomeles japonica) wine by-product.

The wine industry generates large quantities of by-products each year. Therefore, this work aimed to isolate and evaluate the oil and protein fractions of Japanese quince (Chaenomeles japonica, JQ) press residue, offering a partial utilization of valuable bioactive compounds of wine industry by-products. To study the JQ oil extract yield, composition and oxidation stability, we modified the co-solvent composition during the supercritical CO2 (SC-CO2) extraction of oil by adding different ethanol content. The remaining defatted material was used for the isolation of proteins. The SC-CO2 extraction yielded oil rich in polyunsaturated fatty acids, tocopherols, and phytosterols. The use of ethanol as a co-solvent increased the oil yield but did not enhance its oxidative stability or content of antioxidants. We recovered protein isolate after removing tannins with 70% ethanol extraction in the next step. The JQ protein isolate contained all essential amino acids. In addition to its balanced amino acid composition, the protein isolate exhibited excellent emulsifying properties highlighting its potential as a food additive. In conclusion, JQ wine by-products can be utilized for the extraction of oil and protein fractions which can be used in food or cosmetic product formulation.

Free Amino Acids and Biogenic Amines Profiling and Variation in Wild and Sub-Endemic Cardueae Species from Sardinia and Corse.

The cardueae are a common species in the Mediterranean area where they grow spontaneously and are traditionally employed as food and for health purposes. In this work, five Cardueae, including two sub-endemic species (four Carduus and three Ptilostemon casabonae (L.) Greuter samples from different locations) were collected from Sardinia and the Corse islands. All the considered plants are characteristic of the area, in particular the sub-endemic species C. cephalanthus and P. casabonae. This work aims to obtain, for the first time, the amino compounds profile (primary metabolites) of these little-studied species to detect for any similarities and differences among the different samples using statistical analyses. A recently developed method was employed, where diethyl ethoxymethylenemalonate (DEEMM) derivatives are detected in a neutral loss scan mode using high performance liquid chromatography in tandem with a mass spectrometry technique. In total, 42 amino compounds were detected, of which 33 were fully identified and semi-quantified. Overall, the results show that DEEMM-derivatized amino compounds are qualitatively similar among the considered samples. Nonetheless, a discrimination at the genus level is possible. This work adds more information regarding the phytochemical composition regarding the primary metabolites of the considered samples, their discriminations and the search for compounds with potential health benefits.

Higher sirt1 is associated with a better body composition in master sprinters and untrained peers.

Sirt1 is an enzyme involved in several anti-aging pathways. Associations between Sirt1, age, and body fat (BF) were assessed in master sprinters (MS; n = 35; 50.25 ±5.93 yr.), untrained young non-athletes (UY; n = 32; 23.78 ±3.98 yr.), and untrained middle-aged (UMA; n = 24; 47.29 ±8.04 yr.). BF was assessed using a skinfold protocol, and Sirt1 was measured in plasma by using commercial kits. Sirt1 of MS (17.18 ±4.77 ng/mL) was higher than UMA (6.36 ±2.29 ng/mL; p<0.0001) and did not differ from UY (20.26 ±6.20 ng/mL). Relative BF of MS was lower than UMA (12.71 ±4.07% vs. 22.13 ±4.18%; p<0.0001). Sirt1 was negatively correlated with chronological age (r = -0.735; p<0.0001) when combining UY and UMA in the analysis. However, when Sirt1 of MS and UY was analyzed together, no significant relationship between Sirt1 and chronological age was observed (r = -0.243; p = 0.083). Sirt1 correlated inversely with BF (r = -0.743; p<0.0001) for UY and UMA. Stepwise multiple regression revealed that being either a young or master athlete and body adiposity are possible predictors of Sirt1 levels. MS and UY were associated with higher levels of Sirt1, while UMA and increased BF were associated with lower levels of this enzyme. The relationships among Sirt1, BF, and chronological age of young and middle-aged non-athletes were not statistically significant when the middle-aged participants were MS. These findings suggest possible links between Sirt1 and body composition, which may play roles in the rate of biological aging.HighlightsLower levels of Sirt1 are associated with higher body fat.Master athlete lifestyle seems to promote higher Sirt1 Levels.

Sex differences on the response to antidepressants and psychobiotics following early life stress in rats.

Major depressive disorder (MDD) is the most prevalent mood disorder globally. Most antidepressants available for the treatment of MDD increase the concentration of monoamines in the synaptic cleft. However, such drugs have a high latency time to obtain benefits. Thus, new antidepressants with fast action and robust efficacy are very important. This study evaluated the effects of escitalopram, ketamine, and probiotic Bifidobacterium infantis in rats submitted to the maternal deprivation (MD). MD rats received saline, escitalopram, ketamine, or probiotic for 10, 30, or 50 days, depending on the postnatal day (PND):21, 41, and 61. Following behavior, this study examined the integrity of the blood-brain barrier (BBB) and oxidative stress markers. MD induced depressive-like behavior in females with PND21 and males with PND61. All treatments reversed depressive-like behavior in females and escitalopram and ketamine in males. MD induced an increase in the permeability of the BBB, an imbalance between oxidative stress and antioxidant defenses. Treatments regulated the oxidative damage and the integrity of the BBB induced by MD. The treatment with escitalopram, ketamine, or probiotics may prevent behavioral and neurochemical changes associated with MDD, depending on the developmental period and gender.

Combination of electroconvulsive stimulation with ketamine or escitalopram protects the brain against inflammation and oxidative stress induced by maternal deprivation and is critical for associated behaviors in male and female rats.

This study aimed at evaluating the treatment effects with ketamine, electroconvulsive stimulation (ECS), escitalopram, alone or in combination in adult rats of both sexes, subjected to the animal model of maternal deprivation (MD). All groups were subjected to the forced swimming test (FST), splash and open field tests. The prefrontal cortex (PFC), hippocampus and serum were collected to analyze oxidative stress and inflammatory parameters. MD induced depressive-like behavior in the FST test in males and reduced grooming time in male and female rats. The treatments alone or combined reversed depressive and anhedonic behavior in females. In males, all treatments increased grooming time, except for ECS + escitalopram + ketamine. MD increased lipid peroxidation and protein carbonylation, nitrite/nitrate concentration and myeloperoxidase activity in the PFC and hippocampus of males and females. However, the treatment's response was sex dependent. Catalase activity decreased in the PFC of males and the PFC and hippocampus of females, and most treatments were not able to reverse it. MD increased the inflammation biomarkers levels in the PFC and hippocampus of males and females, and most treatments were able to reverse this increase. In all groups, a reduction in the interleukin-10 levels in the PFC and hippocampus of female and male rats was observed. Our study shows different responses between the sexes in the patterns evaluated and reinforces the use of the gender variable as a biological factor in MDD related to early stress and in the response of the therapeutic strategies used.

Telomere Length, SIRT1, and Insulin in Male Master Athletes: The Path to Healthy Longevity?

Lower SIRT1 and insulin resistance are associated with accelerated telomere shortening. This study investigated whether the lifestyle of master athletes can attenuate these age-related changes and thereby slow aging. We compared insulin, SIRT1, and telomere length in highly trained male master athletes (n=52; aged 49.9±7.2 yrs) and age-matched non-athletes (n=19; aged 47.3±8.9 yrs). This is a cross-sectional study, in which all data were collected in one visit. Overnight fasted SIRT1 and insulin levels in whole blood were assessed using commercial kits. Relative telomere length was determined in leukocytes through qPCR analyses. Master athletes had higher SIRT1, lower insulin, and longer telomere length than age-matched non-athletes (p<0.05 for all). Insulin was inversely associated with SIRT1 (r=-0.38; p=0.001). Telomere length correlated positively with SIRT1 (r=0.65; p=0.001), whereas telomere length and insulin were not correlated (r=0.03; p=0.87). In conclusion, master athletes have higher SIRT1, lower insulin, and longer telomeres than age-matched non-athletes. Furthermore, SIRT1 was negatively associated with insulin and positively associated with telomere length. These findings suggest that in this sample of middle-aged participants reduced insulin, increased SIRT1 activity, and attenuation of biological aging are connected.

Is lifelong endurance training associated with maintaining levels of testosterone, interleukin-10, and body fat in middle-aged males?

BACKGROUND: Aging is associated with a gradual physiological decline, including an imbalance in hormone profile, increased adiposity, and reduced anti-inflammatory cytokines. However, lifelong physical exercise mitigates aging, as observed in endurance-trained middle-aged athletes (EMA). AIM: We compared and associated testosterone, interleukin 10 (IL-10), and body fat in EMA and untrained age-matched individuals (UAM). METHODS: Participants were EMA (n=25; 51.48±9.49 years) and UAM (n=23; 46.0±9.37 years). Both groups underwent body composition measurements (evaluated by a skinfold protocol) and blood sampling for IL-10 (assessed through ELISA® kit) and testosterone (assessed with Roche Diagnostics® kit, Mannheim, Germany, by chemiluminescence technique in a third-party laboratory). RESULTS: EMA had lower body fat (14.15±3.82% vs. 23.42±4.95%; P<0.05), higher testosterone (751.68±191.45 ng/dL vs. 493.04±175.15 ng/dL; P<0.05), and higher IL-10 (8.00±1.21 pg/mL vs. 5.89±1.16 pg/mL; P<0.05) compared to UAM. A significant linear correlation was found between testosterone and IL-10 (r=0.56; P=0.001), whereas significant inverse correlations were observed between body fat and testosterone (r=-0.52; P=0.001) and body fat and IL-10 (r=-0.69; P=0.001). CONCLUSIONS: EMA had higher levels of IL-10 and testosterone and lower body fat in comparison with UAM. In addition, higher IL-10 was associated with increased levels of circulating testosterone and lower body fat. RELEVANCE FOR PATIENTS: The adoption of endurance training as part of a healthy lifestyle may contribute to decreasing age-related testosterone reduction, besides reducing markers of inflammaging, preventing the occurrence of chronic age-related diseases, and thus contributing to healthy aging. For people who already have chronic diseases, physical exercise can shift the immune system toward a more anti-inflammatory profile and, thus, improve their pathological condition. In both cases, physical exercise can help attenuate the decline in testosterone, decrease body fat, and increase anti-inflammatory levels.

Derivatization-targeted analysis of amino compounds in plant extracts in neutral loss acquisition mode by liquid chromatography-tandem mass spectrometry.

Amino compounds, such as amino acids and biogenic amines, are important metabolites that can be found in diverse natural matrices. The most common method for amino compound analysis nowadays is reversed-phase liquid chromatography tandem mass spectrometry (RPLC-MS/MS). However, due to the polar and the basic nature of amines, their RPLC retention is often insufficient or peaks are tailing. Derivatization is a way to overcome the issue and in the present work amino compounds are derivatized with diethyl ethoxymethylenemalonate (DEEMM) and analyzed by a RPLC triple quadrupole MS system in neutral loss scan (NLS) mode (loss of 46). This allows to target all compounds in the sample that undergo derivatization with DEEMM, so that the amino compound profile of the sample is obtained. To the best of our knowledge, the NLS acquisition mode has never been employed to target amino compounds after DEEMM derivatization. In the first part of the study, eight amino acids (arginine, aspartic acid, threonine, proline, tyrosine, tryptophan, phenylalanine and isoleucine) were employed as model compounds for method optimization, with good results in terms of DEEMM derivatives detection and repeatability. The developed method was successfully applied to a complex extract from the plant species Carduus nutans subsp. macrocephalus (Desf.) Nyman, with 18 amino acids and 3 other amines being identified. The proposed approach could be employed for straightforward identification of known and unknown amino compounds in different types of matrices.

Development and validation of the Perceived Influences on Sport and Study Assessment Scale / Desenvolvimento e validação da Escala de Avaliação de Influências Percebidas no Esporte e no Estudo / Desarrollo y validación de la Escala de Evaluación de Influencias Percibidas en el Deporte y en el Estudio

The objective of this cross-sectional study was to develop and validate an Assessment Scale for Perceived Influences in Sport and Study (EIPE). The validation process was carried out with specialists and athletes of both sexes, from team and individual sports, aged between 13 and 18 years old and who attended secondary and high school Education in Santa Catarina/Brazil. Five steps were taken in order to validate the instrument: content validity; clarity of language; pilot test; construct validity; internal consistency; and reliability. Results showed that the final version of the EIPE (two factors and 49 items) showed satisfactory adjustment indices (χ2/gl = 1.751; GFI = .85; AGFI = .82; CFI = .90; SRMR = .059; RMR = .046; RMSEA = .042; CFI = .90; TLI = .89), high internal consistency (α > .70) and reliability (α > .91). It is concluded that the EIPE has satisfactory psychometric properties that provide evidence of scientific validity and reliability. (AU)

O objetivo desse estudo foi desenvolver e validar uma Escala de Avaliação de Influências Percebidas no Esporte e no Estudo (EIPE). O processo de validação foi realizado com especialistas e atletas de ambos os sexos, com idade entre 13 e 18 anos e que cursavam a Educação Básica em Santa Catarina/Brasil. Cinco etapas foram realizadas para validar o instrumento: validade de conteúdo; clareza de linguagem; teste de piloto; validade do construto; consistência interna; e fidedignidade. Os resultados mostraram que a versão final da EIPE (dois fatores e 49 itens) apresentou índices de ajuste satisfatórios (χ2/gl = 1,751; GFI = 0,85; AGFI = 0,82; CFI = 0,90; SRMR = 0,059 ; RMR = 0,046; RMSEA = 0,042; CFI = 0,90; TLI = 0,89), alta consistência interna (α > 0,70) e fidedignidade (α > 0.91). Conclui-se que a EIPE possui propriedades psicométricas aceitáveis que fornecem evidências de validade e confiabilidade científica. (AU)

El objetivo de este estudio fue desarrollar y validar una Escala de evaluación de las influencias percibidas en el deporte y el estudio (EIPE). El proceso de validación se llevó a cabo con especialistas y atletas de ambos sexos, con edades entre 13 y 18 años, que estudiaban Educación Básica en Santa Catarina/Brasil. Se dieron cinco pasos para validar el instrumento: validez de contenido; claridad del lenguaje; prueba piloto; validez de constructo; consistencia interna; y fiabilidad. Los resultados mostraron que la versión final del EIPE (dos factores y 49 ítems) mostró índices de ajuste satisfactorios (χ2/gl = 1.751; GFI = .85; AGFI = .82; CFI = .90; SRMR = .059; RMR = .046; RMSEA = .042; CFI = .90; TLI = .89), alta consistencia interna (α > .70) y fiabilidad (α > .91). Se concluye que el EIPE tiene propiedades psicométricas aceptables que proporcionan evidencia de validez y confiabilidad científica. (AU)

A second generation of 1,2,4-oxadiazole derivatives with enhanced solubility for inhibition of 3-hydroxykynurenine transaminase (HKT) from Aedes aegypti.

The most widely used method for the control of the Aedes aegypti mosquito population is the chemical control method. It represents a time- and cost-effective way to curb several diseases (e.g. dengue, Zika, chikungunya, yellow fever) through vector control. For this reason, the discovery of new compounds with a distinct mode of action from the available ones is essential in order to minimize the rise of insecticide resistance. Detoxification enzymes are an attractive target for the discovery of new insecticides. The kynurenine pathway is an important metabolic pathway, and it leads to the chemically stable xanthurenic acid, biosynthesized from 3-hydroxykynurenine, a precursor of reactive oxygen and nitrogen species, by the enzyme 3-hydroxykynurenine transaminase (HKT). Previously, we have reported the effectiveness of 1,2,4-oxadiazole derivatives acting as larvicides for A. aegypti and AeHKT inhibitors from in vitro and in silico studies. Here, we report the synthesis of new sodium 4-[3-(aryl)-1,2,4-oxadiazol-5-yl] propanoates and the cognate HKT-inhibitory activity. These new derivatives act as competitive inhibitors with IC50 values in the range of 42 to 339 µM. We further performed molecular docking simulations and QSAR analysis for the previously synthesized sodium 4-[3-(aryl)-1,2,4-oxadiazol-5-yl] butanoates reported earlier by our group and the data produced herein. Most of the 1,2,4-oxadiazole derivatives, including the canonical compounds for both series, showed a similar binding mode with HKT. The binding occurs similarly to the co-crystallized inhibitor via anchoring to Arg356 and positioning of the aromatic ring and its substituents outwards at the entry of the active site. QSAR analysis was performed in search of more than 770 molecular descriptors to establish a relationship between the lowest energy conformations and the IC50 values. The five best descriptors were selected to create and validate the model, which exhibited parameters that attested to its robustness and predictability. In summary, we observed that compounds with a para substitution and heavier groups (i.e. CF3 and NO2 substituents) had an enhanced HKT-inhibition profile. These compounds comprise a series described as AeHKT inhibitors via enzymatic inhibition experiments, opening the way to further the development of new substances with higher potency against HKT from Aedes aegypti.

Relationship between inflammatory biomarkers and testosterone levels in male master athletes and non-athletes.

BACKGROUND: Aging is often associated with low-grade systemic inflammation and reduced anabolic hormone levels. To investigate whether lifelong exercise training can decrease the age-related low-grade inflammation and anabolic hormone levels, we examined hormonal and inflammatory parameters among highly-trained male masters athletes and age-matched non-athletes. METHODS: From 70 elite power and endurance master athletes - EMA (51.3 ± 8.0 yr), 32 young controls - YC (23.7 ± 3.9 yr) and 24 untrained age-matched controls - MAC (47.2 ± 8.0 yr) venous blood was drawn to measure inflammatory parameters (interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α] and interleukin-10 [IL-10]) and circulating hormones (luteinizing hormone [LH], total testosterone, estradiol, sex hormone-binding globulin [SHBG] and free androgen index [FAI]). RESULTS: EMA showed a better anti-inflammatory status than MAC (higher IL-10 and IL-10/IL-6 ratio and lower IL-6), but a lower anti-inflammatory status than YC (higher TNF-α) (p < 0.05). The MAC group had lower testosterone levels compared to the YC and EMA group (p < 0.05), and lower estradiol levels and testosterone/LH ratio compared to YC (p < 0.05). In the control groups (MAC and YC), testosterone correlated negatively with age and proinflammatory parameters, and positively with anti-inflammatory parameters. CONCLUSION: Elite master athletics elevated levels of anti-inflammatory cytokines above that seen in non-athlete peers and mitigated the age-related reduction in testosterone levels.

Age-related Decline in Renal Function is Attenuated in Master Athletes.

This study analyzed the kidney function and biomarkers of health in lifelong-trained sprinters and endurance runners, and compared them to untrained aged-matched and young controls. Sixty-two men (21-66 yr.) were recruited and allocated as master athletes from sprints (n=25), master athletes from endurance events (n=8), untrained middle-aged (n=14) and young controls (n=15). Participants underwent anamnesis, anthropometric measures and blood sampling for biochemical analyses of klotho, FGF23 and estimated glomerular filtration rate. Master sprinters presented better kidney function in relation to endurance athletes and their untrained peers (P<0.0001). A number of biochemical variables were observed that negatively (i. e., GDF-15, TGF-Beta, IL-18) or positively (i. e., klotho/FGF23 ratio and sestrin-2) correlated with eGFR. Sestrin-2 presented the strongest association with eGFR (r=0.5, P=0.03). Results also revealed that lifelong-trained individuals presented the highest probability of having better values for cystatin C and thus an estimated glomerular filtration rate that was 37-49% higher than untrained peers. Master sprinters presented better kidney function in relation to endurance athletes and middle-aged untrained peers. Sestrin-2 may play a role in exercise-induced kidney function protection.

Master athletes have longer telomeres than age-matched non-athletes. A systematic review, meta-analysis and discussion of possible mechanisms.

The aim of this systematic review and meta-analysis was 1) to assess whether master athletes have longer telomeres than age-matched non-athletes and 2) discuss possible underlying mechanisms underlying telomere length preservation in master athletes. A literature search was performed in PubMed, Web of Science, Scopus and SPORTDiscus up to August 2020. Only original articles published in peer-reviewed journals that compared telomere length between master athletes and aged-matched non-athletes were included. Eleven studies fulfilled eligibility criteria and were included in the final analysis. Overall, 240 master athletes (51.9±7.5 years) and 209 age-matched non-athletes (50.1±9.1 years) were analyzed. Master athletes had been participating in high-level competitions for approximately 16.6 years. Pooled analyses revealed that master athletes had longer telomeres than aged-matched non-athletes (SMD=0.89; 95% CI=0.45 to 1.33; p<0.001). Master athletes showed lower pro-oxidant damage (SMD=0.59; 95% CI=0.26 to 0.91; p<0.001) and higher antioxidant capacity (SMD=-0.46; 95% CI=-0.89 to -0.03; p=0.04) than age-matched non-athletes. Further, greater telomere length in master athletes is associated with lower oxidative stress and chronic inflammation, and enhanced shelterin protein expression and telomerase activity. In conclusion, 1) master athletes have longer telomeres than age-matched non-athletes, which may be the result of 2) lower levels of oxidative stress and chronic inflammation, and elevated shelterin expression and telomerase activity.