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The physicochemical changes induced by seven different dietary fibers (oat, bamboo, pea, inulin, apple, potato, and wheat) during storage and their effects on the survival of homofermentative Lacticaseibacillus casei subsp. casei (L. casei) in fermented milk matrix were analyzed. For this, an experimental study of the effect of storage time on the microorganisms count and physicochemical properties (pH, titratable acidity, syneresis and viscosity) of milk fermented with L. casei was carried out every two weeks during a storage period of 42 days. Throughout the period studied at 4 °C, no significant differences were found in terms of viscosity values, syneresis rates and L. casei counts, despite the substantial decrease in the pH values. Notably, the substantial increase in the concentration of free hydronium ions (active acidity) in the fiber-enriched matrices during the follow-up period was positively correlated with the L.casei survival. The microbial count determined in all samples was higher than 1 × 107 CFU/g, the minimum value recommended by world organizations for nutraceutical fermented foods. Consequently, the studied prebiotic fibers could be considered in the production of new fermented dairy products with functional properties. Graphical abstract

This study evaluated the effects of long-term intake of nutritive sweeteners (NSs) and non-nutritive sweeteners (NNSs) on body weight, food and energy intake, blood pressure, metabolic parameters, and memory retention in rats. Sixty male Sprague-Dawley rats were randomly divided into six groups (

We examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

Introduction: obesity is a cardiometabolic risk (CMR) factor in adolescents. It represents a public health problem that requires simple diagnostic strategies based on the determination of anthropometric indicators (AIs) such as body mass index (BMI), waist circumference (WC), conicity index (CONI), waist-to-height ratio (WHtR), and body fat percentage (BFP). The purpose of the current contribution was to analyze the utility of the aforementioned AIs for evaluating obesity as a CMR factor in Mexican adolescents. Materials and methods: the design of the study is descriptive and cross-sectional. Nutritional status was established by using various AIs and as a CMR factor under the criteria of WHtR. Participating in the present investigation were 2,000 adolescents from 15 to 17 years of age, of which 1,079 (53.9 %) were female and 921 (46.1 %) were male. All were high school students in Tuxtla Gutiérrez, Chiapas, Mexico. Results and conclusion: the prevalence of obesity was influenced by gender. With the WHtR and BFP, male students exhibited a greater prevalence of obesity, while with the BMI and CONI, the percentage of obesity was similar between the two genders. BMI was significantly correlated with BFP, WC and WHtR, and was one of the AIs with the greatest area under the curve, showing a good capacity to predict cardiometabolic risk. BMI is a simple and adequate tool for diagnosing obesity and predicting CMR in adolescents.Introducción: la obesidad es un factor de riesgo cardiometabolico (RCM) en los adolescentes y representa un problema de salud pública que requiere estrategias diagnosticas sencillas, basadas en la determinación de indicadores antropométricos (IA) como el índice de masa corporal (IMC), la circunferencia de la cintura (CC), el índice de conicidad (ICONI), el índice de cintura-talla (ICT) y el porcentaje de grasa corporal (PGC). El propósito del presente estudio fue analizar la utilidad de diversos IA (IMC, CC, ICONI, ICT y PGC) para evaluar la obesidad como factor de RCM en adolescentes mexicanos. Materiales y métodos: el diseño del estudio fue descriptivo y transversal. Se analizó el estado nutricional mediante varios IA y el factor de RCM bajo los criterios del ICT. Este estudio fue conducido en 2000 adolescentes de entre 15 y 17 años, de los cuales 1079 (53,9 %) eran mujeres y 921 (46,1 %) varones, todos ellos estudiantes de nivel medio superior de Tuxtla Gutiérrez, Chiapas, México. Resultados y conclusión: la prevalencia de la obesidad estuvo influenciada por el género: los varones presentaron una mayor prevalencia de obesidad con ICT y PGC, mientras que con IMC e ICONI, el porcentaje de obesidad fue similar entre ambos géneros. El IMC se correlacionó significativamente con el PGC, la CC y el ICT, y fue uno de los IA con mayor área bajo la curva, mostrando una buena capacidad para predecir el RCM. El IMC representa una herramienta sencilla y adecuada para el diagnóstico de obesidad y predecir el RCM en adolescentes.

We examined in a rat model of Gulf War illness (GWI), the potential of (-)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicles and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

Major depression is one of the most common affective disorders caused by schizophrenia. The administration of N-methyl-D-aspartate receptor antagonists, such as ketamine, can reproduce the negative and affective symptoms of this disorder in animals. Preclinical studies have shown that 5-HT6 receptor (5-HT6R) agonists and antagonists have a considerable antipsychotic response. The aim of the present study was to evaluate the effect of an acute treatment with an agonist, E-6837, and an antagonist, SB-271046, of 5-HT6R on the immobility induced in mice by a subchronic ketamine regimen (5 days; 10 mg/kg/day, intraperitoneal). Repeated ketamine administration alone increased the immobility time in the forced-swimming test and the tail-suspension test. E-6837 at 10 and 20 mg/kg caused a significant reduction of immobility in the tail-suspension test and forced-swimming test, respectively. Interestingly, SB-271046 (10 mg/kg) also elicited an antidepressant-like effect in both tests. The current findings suggest an important role for these 5-HT6R ligands as mood modulators. However, it is necessary to explore the physiological mechanisms involved in this process in greater detail.

In recent years, it has been shown that histone deacetylase 2 (HDAC2) inhibitors increase histone acetylation and enhance memory processes, probably due to an increase in the gene transcription rate that emerges during memory formation. Histone acetylation generally favors long-term memory, whereas histone deacetylation impinges on it. However, until today there is no specific drug that can target the HDAC2 active site. In this work we applied the method of rational drug design, through enzyme-structural-chemical properties to generate new molecules as HDAC inhibitors. By the application of Quantitative Structure-Activity Relationship (QSAR) and molecular modeling methodologies our aim is to predict more potent HDAC inhibitors. 76 small molecules with potential activity were analyzed using QSAR methodology. The best model was constructed by merging the properties of electronegativity, atomic mass, polarizability, van der Waals forces and some conformational aspects, with the following statistical parameters: r 2 = 0.8935, q 2 LOO-CV = 0.8498, and q 2 LGO-CV = 0.7598. The molecular docking of the ligands on the template was performed by blind docking. The results showed intermolecular interactions between small molecules and some amino acids, such as His145, His146, Asp179, Asp186, and internal-H2O and Zn2+ of which IN01, IN04, and IN14 showed theoretically better biological activity compared with that of TSA and SAHA. Mainly, the IN14 synthesized molecule is a theoretical inhibitor of HDAC class I.

One of the main hallmarks of Alzheimer's disease includes the neurofibrillary tangles formation produced by hyperphosphorylation of the Tau protein, whose expression is putatively regulated by the ovarian hormones estradiol and progesterone. Hippocampus is a brain region that participates in many functions related to learning and memory; in addition, it is abundant in both estradiol and progesterone receptors. In this study, we explore the expression of Tau hyperphosphorylation at hippocampus and the performance of rats in an autoshaping learning task at 5, 10 and 15 months after the ovaries removal. In these animals, ovariectomy was performed at 3 months of age. These data were compared with those derived from intact rats at 8, 13 and 18 months old. A clear decrease in the number of conditioned responses of both intact and ovariectomized rats in the autoshaping learning task was observed. The interaction of both factors confirms that, in this test, learning varies depending on aging and the presence or absence of ovaries. A progressive increase in hippocampal Tau phosphorylation at Ser-396 was observed in either intact or ovariectomized rats. Interestingly, an interaction between the analyzed factors shows that such hyperphosphorylation was potentiated by the absence of ovaries. These results emphasize the importance of aging and the lack of ovarian hormones for an associative learning test and for the expression of one of the most important hallmarks of Alzheimer's disease.

espanolIntroduccion: los indicadores antropometricos (IA) como la circunferencia de cintura (CC), el indice de masa corporal (IMC), el indice cintura/ cadera (ICC), el indice cintura/talla (ICT) y el porcentaje de grasa corporal (PGC) son herramientas utiles para el diagnostico del estado nutricional (EN) en los adolescentes. Sin embargo, cada uno de estos IA presentan ventajas y desventajas. El proposito del presente estudio fue analizar la asociacion de los IA (IMC, CC, ICC, ICT y PGC) para evaluar el EN y estimar el riesgo cardiometabolico (RCM) en adolescentes mexicanos. Material y metodo: el diseno del estudio fue descriptivo transversal. Se analizo el EN a traves de diversos IA y el RCM bajo los criterios de ICT. Este estudio fue conducido en 917 adolescentes de entre 15 y 17 anos, de los cuales 488 (52,9%) eran mujeres y 429 (47,1%) varones, todos estudiantes de nivel medio superior de Tuxtla Gutierrez, Chiapas, Mexico. Resultados y conclusion: las mujeres presentaron mayor prevalencia de obesidad con la mayoria de los IA utilizados. El ICT fue el IA que detecto mayor prevalencia de obesidad (31%), correlacionandose con el IMC y el PGC. Ademas, se evidencio una asociacion significativa entre el EN valorado por todos los IA y el RCM. El ICT podria ser considerado como una herramienta adecuada para el diagnostico de obesidad asociada a RCM en adolescentes. EnglishIntroduction: anthropometric indicators (AIs) such as waist circumference (WC), body mass index (BMI), waist/hip index (WHpI), waist/height index (WHtI) and body fat percentage (BFP) are useful tools for the diagnosis of nutritional status (NS) in adolescents. Each of these parameters has advantages and disadvantages. The purpose of the present study was to analyze the association of these AIs (WC, BMI, WHpI, WHtI, and BFP) to evaluate nutritional status and estimate the cardiometabolic risk (CMR) in Mexican adolescents. Material and method: in a cross-sectional descriptive study, the NS was analyzed through various AIs and CMR with the WHtI criteria. Nine hundred and seventeen adolescents between 15 and 17 years old participated in the study, of whom 488 (52.9%) were female and 429 (47.1%) male, all students of middle school in Tuxtla Gutierrez, Chiapas, Mexico. Results and conclusion: women presented a higher prevalence of obesity according to most indicators. The WHtI was the parameter that detected the highest prevalence of obesity (31%), correlating with the BMI and the BFP. Moreover, there was evidence of a significant relation between NS (assessed by all the anthropometric indicators) and CMR. The WHtI could be considered as an adequate tool for the diagnosis of obesity associated with CMR in adolescents.

Treatment with 17-β estradiol and progesterone improves the performance of ovariectomized rats in an autoshaping learning task, representing cognitive improvement. To test whether this is attributable to genomic mechanisms, the antiestrogen ICI 182 780 or antiprogesterone RU486 was injected into ovariectomized animals primed previously with estrogen or progesterone, respectively. Compared with the vehicle control, each hormone administered alone produced an elevated expression of choline acetyltransferase and TrkA, along with an improvement in performance on the behavioral test. E2+ICI reverted the increase in these two proteins. However, RU alone elicited higher ChAT expression. With this exception, there was a clear linear regression between the number of conditioned responses and the level of ChAT and TrkA in the basal forebrain. The results suggest that TrkA may be more important than ChAT for regulating autoshaping learning tasks, and that genomic mechanisms in the basal forebrain could possibly underlie hormonal improvement of cognition.

The influx/efflux of calcium (Ca2+) ions through channels in cellular membranes plays a pivotal role in many physiological and physiopathological processes. Among these are those involved in the physiopathology of epileptic seizures. Hence, the control of permeability of ions through these channels is considered a strategy for the development of anticonvulsant drugs. According to the previous reports, dihydropyridine derivatives have proven to be Ca2+ channel blockers and have anticonvulsive properties, presumably by means of their action on L-type Ca2+ channels (LCCs). The aim of the present study was to determine the anticonvulsant effects of four bis-1,4-dihydropyridines (bis-DHPs) in male CF1 mice (25–30 g bw) using two experimental models: maximal electroshock (MES, which induces convulsions with an alternating current of 60 Hz) and pentylenetetrazole administration (PTZ, 90 mg/kg administered i.p.). Additionally, the binding mode was explored with a docking study on a 3-D model of an LCC. The four bis-DHPs herein tested showed a protective effect in relation to the number of convulsions induced by MES, the recovery time after a convulsion, and the duration of the tonic phase. However, only bis-DHPs 01–03 reduced the duration of the clonic phase, and these compounds also produced a significant protective effect against the convulsions induced by PTZ administration. This effect may be related to the interaction of bis-DHPs with a cluster of aromatic residues (Tyr1152, Tyr1463, and Phe1159) involved in blocking calcium flow, as suggested by docking studies.

Hormone replacement therapy (HRT) may be prescribed to prevent the symptoms of menopause. This therapy may include estrogenic and/or progestin components and may increase the incidence of endometrial and breast cancers. Tibolone (TIB), which is also made up of estrogen and progestin components, is often used to reduce the impact of HRT. However, the effect of TIB on the processes of learning, memory and anxiety has yet to be fully elucidated. The aim of this study was to evaluate the long-term effect on learning, memory processes and anxiety in ovariectomized rats caused by different doses of TIB (0 mg/kg, 0.01 mg/kg, 0.1 mg/kg 1.0 mg/kg and 10 mg/kg, administered daily via the oral route for 18 weeks). Two behavioral animal models, the autoshaping and T maze models were employed. The concentrations of acetyl choline transferase (ChAT) and tryptophan hydroxylase (TPH) in the hippocampus were directly measured by Western blot. No significant changes were observed in the autoshaping model and spontaneous activity test. In the T maze, increased latency was observed with TIB doses of 1 and 10 mg/kg compared to the vehicle. We observed that the ChAT content decreased with increasing doses of TIB, whereas TPH content increased with doses of 1 and 10 mg/kg of TIB. These data indicate that high doses of TIB improved emotional learning, which may be related to the modulation of the cholinergic and serotonergic systems by TIB.

Aims We analyzed the effects of the short- and long-term administration of estradiol (E2) or progesterone (P4) after ovariectomy on the expression of MAP2, Tau and GFAP in prefrontal cortex and hippocampus. Main methods Sprague Dawley rats were ovariectomized and immediately treated with E2 or P4 for 2 or 18 weeks. At the end of treatments, hippocampus and prefrontal cortex were excised, proteins were extracted and MAP2, Tau and GFAP were analyzed by Western blot. Key findings MAP2 and Tau content was not modified by E2 in the prefrontal cortex. On the contrary, P4 decreased MAP2 content after a short-term treatment, while it increased that of MAP2 and TAU in this brain region after a long-term treatment. E2 increased MAP2 content in hippocampus. In this region, short-term administration of P4 increased that of MAP2. GFAP content was diminished after a long-term administration of P4 in hippocampus. Significance Current data emphasize the importance of short- and long-term sex steroid treatment on neuronal and glial cytoskeletal proteins expression.

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone (TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB (0.01 mg/kg and 1 mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau (PHF-1) proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

It has been proposed that sex steroid hormones improve performance in some cognitive tasks by regulating the basal forebrain cholinergic function. However, the molecular basis of such influence still remains unknown. Current study analyzed the performance of ovariectomized rats in an autoshaping learning task after a short-term treatment with 17β-estradiol (E2: 4 and 40μg/kg) and/or progesterone (P4: 4mg/kg). These results were correlated with basal forebrain choline acetyltransferase (ChAT) and TrkA protein content. The high dose of E2 enhanced both acquisition in the autoshaping task and the content of ChAT and TrkA. P4 treatment increased ChAT and TrkA content without affecting performance of rats in the autoshaping learning task. Interestingly, the continuous and simultaneous administration of E2 plus P4 did not significantly modify behavioral and biochemical evaluated parameters. These results address the influence of both E2 and P4 on cholinergic and TrkA activity and suggest that the effects of ovarian hormones on cognitive performance involve basal forebrain cholinergic neurons.

It is well accepted that acetylcholine is involved in memory and learning processes and that loss of memory is characteristic of Alzheimer's disease (AD). Several muscarinic agonists have been shown to be clinically effective in the treatment of AD. However, their use has been limited due to adverse side effects. As a result, more selective M1 agonists are expected to be the next generation of agents for the treatment of AD. One pharmacological approach to evaluate possible cognitive effects of compounds includes their ability to reverse scopolamine-induced amnesia. In the current study the succinamide and succinimide of p-aminophenol, two newly synthesized compounds that were previously designed to be acetylcholine analogues, were evaluated in a Pavlovian/Instrumental autoshaped memory task. Simultaneously, docking studies on the M1 receptor were done. The scopolamine-induced amnesia was reversed by the amide but not the imide. These findings are in line with results derived from the docking simulations, and suggest that at least the succinamide of p-aminophenol could represent a novel candidate for the treatment of AD.

Two arylderivatives, 3a-Acetoxy-5H-pyrrolo(1,2-a) (3,1)benzoxazin-1,5-(3aH)-dione 3 and cis-N-p-Acetoxy-phenylisomaleimide 4, were synthesized from anthranilic acid and para-aminophenol, respectively. The inhibitory effects of these compounds on acetylcholinesterase (AChE) activity were evaluated in vitro as well as by docking simulations. Both compounds showed inhibition of AChE activity (Ki = 4.72 +/- 2.3 microM for 3 and 3.6 +/- 1.8 microM for 4) in in vitro studies. Moreover, they behaved as irreversible inhibitors and made pi-pi interaction with W84 and hydrogen bonded with S200 and Y337 according to experimental data and docking calculations. The docking calculations showed deltaG bind (kcal/mol) of - 9.22 for 3 and - 8.58 for 4. These two compounds that can be use as leads for a new family of anti-Alzheimer disease drugs.

p-Aminobenzoic acid (p-ABA) derivatives were evaluated as acetylcholinesterase inhibitors (AChEIs). Finding a correlation between AChE activity with the partition coefficient (log P) and the highest occupied molecular orbital (HOMO) energy of the compounds.

p-Aminobenzoic acid (p-ABA) derivatives were evaluated as acetylcholinesterase inhibitors (AChEIs). Finding a correlation between AChE activity with the partition coefficient (log P) and the highest occupied molecular orbital (HOMO) energy of the compounds.