Unraveling the non-fitness status of NK cells: Examining the NKp30 receptor and its isoforms distribution in HIV/HCV coinfected patients.

BACKGROUND: HIV/HCV coinfection is associated with a rapid progression to liver damage. Specifically, NK cell population dysregulation is of particular interest, as these cells have been shown to block HCV replication effectively and have an anti-fibrogenic activity. The NKp30 receptor is linked to tumor cell lysis and has a crucial role during viral infections. In the present study, we determined the subpopulations of NK cells based on CD56 and CD16 expression, NKp30 receptor expression, its isoforms A, B, and C, along with the cytotoxicity molecules in patients with HIV/HCV. RESULTS: evidenced by the APRI and FIB-4 indices, the HCV-infected patients presented greater liver damage than the HIV and HIV/HCV groups. The HCV group presented a decreased expression of NKp30 isoform A, and NK cell frequency was not different between groups; however, CD56brigth subpopulation, NKp30 receptor, and CD247 adaptor chain were decreased in HIV/HCV patients; further, we described increased levels of soluble IL-8, IL-10, IL-12, and IL-23 in the serum of HIV/HCV patients. CONCLUSIONS: HCV and HIV/HCV patients have multiple parameters of non-fitness status in NK cells; awareness of these dysfunctional immunological parameters in HIV/HCV and HCV patients can elucidate possible novel therapeutics directed towards the improvement of NK cell fitness status, in order to improve their function against liver damage.

The Long Non-Coding RNA MALAT1 Modulates NR4A1 Expression through a Downstream Regulatory Element in Specific Cancer Cell Types.

Long non-coding RNAs (lncRNAs) have been shown to modulate gene expression and are involved in the initiation and progression of various cancer types. Despite the wealth of studies describing transcriptome changes upon lncRNA knockdown, there is limited information describing lncRNA-mediated effects on regulatory elements (REs) modulating gene expression. In this study, we investigated how the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) lncRNA regulates primary target genes using time-resolved MALAT1 knockdown followed by parallel RNA-seq and ATAC-seq assays. The results revealed that MALAT1 primarily regulates specific protein-coding genes and a substantial decrease in the accessibility downstream of the NR4A1 gene that was associated with a decreased NR4A1 expression. Moreover, the presence of an NR4A1-downstream RE was demonstrated by CRISPR-i assays to define a functional MALAT1/NR4A1 axis. By analyzing TCGA data, we identified a positive correlation between NR4A1 expression and NR4A1-downstream RE accessibility in breast cancer but not in pancreatic cancer. Accordingly, this regulatory mechanism was experimentally validated in breast cancer cells (MCF7) but not in pancreatic duct epithelial carcinoma (PANC1) cells. Therefore, our results demonstrated that MALAT1 is involved in a molecular mechanism that fine-tunes NR4A1 expression by modulating the accessibility of a downstream RE in a cell type-specific manner.

The sodium-proton exchangers sNHE and NHE1 control plasma membrane hyperpolarization in mouse sperm.

Sperm capacitation, crucial for fertilization, occurs in the female reproductive tract and can be replicated in vitro using a medium rich in bicarbonate, calcium, and albumin. These components trigger the cAMP-PKA signaling cascade, proposed to promote hyperpolarization of the mouse sperm plasma membrane through activation of SLO3 K+ channel. Hyperpolarization is a hallmark of capacitation: proper membrane hyperpolarization renders higher in vitro fertilizing ability, while Slo3 KO mice are infertile. However, the precise regulation of SLO3 opening remains elusive. Our study challenges the involvement of PKA in this event and reveals the role of Na+/H+ exchangers. During capacitation, calcium increase through CatSper channels activates NHE1, while cAMP directly stimulates the sperm-specific NHE, collectively promoting the alkalinization threshold needed for SLO3 opening. Hyperpolarization then feeds back Na+/H+ activity. Our work is supported by pharmacology, and a plethora of KO mouse models, and proposes a novel pathway leading to hyperpolarization.

Biological properties of stem cells from the apical papilla exposed to lipopolysaccharides: An in vitro study.

OBJECTIVE: The aim of this study was to analyze the effect of lipopolysaccharides (LPS) on the biological properties of stem cells from the apical papilla (SCAPs), such as viability, adhesion to dentin, odontoblast-like differentiation, mineralization, and release of immunomodulatory cytokines. DESIGN: SCAPs were isolated from immature teeth of three donors (10 to 15 years old) and cultured in mineralizing media with or without 1 µg/mL lipopolysaccharide (LPS). Cells were seeded and cultured under standardized conditions; viability was assessed by MTT assay on days 1, 3, 5, and 7; adhesion to dentin was analyzed using an environmental scanning electron microscope after 2 days; the expression of odontogenic and mineralization genes (DSPP, DMP-1, OCN, Col1A1) was evaluated through qPCR after 14 days, mineralization was evaluated with alizarin red staining after 21 days; and the release of immunomodulatory cytokines (IL-6 and IL-10) was measured by ELISA after 1 and 7 days. The Kruskal-Wallis test was performed to detect the effect of LPS on SCAPs, followed by the Dunn-Sidak test. RESULTS: LPS presence in the culture media affected SCAPs viability on day 5 and increased IL-6 secretion by day 7, however, SCAPs retained the adhesion to dentin and mineralization capacities, as well as the differentiation capacity into a mineralizing phenotype. CONCLUSION: In conclusion, within the limitations of this in vitro study, and under the inflammatory microenvironment simulated in this study, stem cells from the apical papilla were found with retained adhesion capacity to dentin, differentiation into a mineralizing phenotype, mineralization, and release of IL-10.

Comprehensive Development of a Cellulose Acetate and Soy Protein-Based Scaffold for Nerve Regeneration.

BACKGROUND: The elaboration of biocompatible nerve guide conduits (NGCs) has been studied in recent years as a treatment for total nerve rupture lesions (axonotmesis). Different natural polymers have been used in these studies, including cellulose associated with soy protein. The purpose of this report was to describe manufacturing NGCs suitable for nerve regeneration using the method of dip coating and evaporation of solvent with cellulose acetate (CA) functionalized with soy protein acid hydrolysate (SPAH). METHODS: The manufacturing method and bacterial control precautions for the CA/SPAH NGCs were described. The structure of the NGCs was analyzed under a scanning electron microscope (SEM); porosity was analyzed with a degassing method using a porosimeter. Schwann cell (SCL 4.1/F7) biocompatibility of cell-seeded nerve guide conduits was evaluated with the MTT assay. RESULTS: The method employed allowed an easy elaboration and customization of NGCs, free of bacteria, with pores in the internal surface, and the uniform wall thickness allowed manipulation, which showed flexibility; additionally, the sample was suturable. The NGCs showed initial biocompatibility with Schwann cells, revealing cells adhered to the NGC structure after 5 days. CONCLUSIONS: The fabricated CA/SPAH NGCs showed adequate features to be used for peripheral nerve regeneration studies. Future reports are necessary to discuss the ideal concentration of CA and SPAH and the mechanical and physicochemical properties of this biomaterial.

Modulation of Kynurenic Acid Production by N-acetylcysteine Prevents Cognitive Impairment in Adulthood Induced by Lead Exposure during Lactation in Mice.

Lead (Pb2+) exposure during early life induces cognitive impairment, which was recently associated with an increase in brain kynurenic acid (KYNA), an antagonist of NMDA and alpha-7 nicotinic receptors. It has been described that N-acetylcysteine (NAC) favors an antioxidant environment and inhibits kynurenine aminotransferase II activity (KAT II, the main enzyme of KYNA production), leading to brain KYNA levels decrease and cognitive improvement. This study aimed to investigate whether the NAC modulation of the brain KYNA levels in mice ameliorated Pb2+-induced cognitive impairment. The dams were divided into four groups: Control, Pb2+, NAC, and Pb2++NAC, which were given drinking water or 500 ppm lead acetate in the drinking water ad libitum, from 0 to 23 postnatal days (PNDs). The NAC and Pb2++NAC groups were simultaneously fed NAC (350 mg/day) in their chow from 0 to 23 PNDs. At PND 60, the effect of the treatment with Pb2+ and in combination with NAC on learning and memory performance was evaluated. Immediately after behavioral evaluation, brain tissues were collected to assess the redox environment; KYNA and glutamate levels; and KAT II activity. The NAC treatment prevented the long-term memory deficit exhibited in the Pb2+ group. As expected, Pb2+ group showed redox environment alterations, fluctuations in glutamate levels, and an increase in KYNA levels, which were partially avoided by NAC co-administration. These results confirmed that the excessive KYNA levels induced by Pb2+ were involved in the onset of cognitive impairment and could be successfully prevented by NAC treatment. NAC could be a tool for testing in scenarios in which KYNA levels are associated with the induction of cognitive impairment.

Exploring Schwann Cell Behavior on Electrospun Polyhydroxybutyrate Scaffolds with Varied Pore Sizes and Fiber Thicknesses: Implications for Neural Tissue Engineering.

The placement of a polymeric electrospun scaffold is among the most promising strategies to improve nerve regeneration after critical neurotmesis. It is of great interest to investigate the effect of these structures on Schwann cells (SCs), as these cells lead nerve regeneration and functional recovery. The aim of this study was to assess SC viability and morphology when cultured on polyhydroxybutyrate (PHB) electrospun scaffolds with varied microfiber thicknesses and pore sizes. Six electrospun scaffolds were obtained using different PHB solutions and electrospinning parameters. All the scaffolds were morphologically characterized in terms of fiber thickness, pore size, and overall appearance by analyzing their SEM images. SCs seeded onto the scaffolds were analyzed in terms of viability and morphology throughout the culture period through MTT assay and SEM imaging. The SCs were cultured on three scaffolds with homogeneous smooth fibers (fiber thicknesses: 2.4 µm, 3.1 µm, and 4.3 µm; pore sizes: 16.7 µm, 22.4 µm, and 27.8 µm). SC infiltration and adhesion resulted in the formation of a three-dimensional network composed of intertwined fibers and cells. The SCs attached to the scaffolds maintained their characteristic shape and size throughout the culture period. Bigger pores and thicker fibers resulted in higher SC viability.

Investigating cooperative effects in small cobalt and cobalt-nickel alloy clusters with attached ethanol.

Small cationic cobalt, and cobalt-nickel alloy clusters with ethanol attached are generated in a pulsed molecular beam experiment using a laser ablation source. While the metal center is successively varied with respect to size and composition, a full-size study of these transition metal clusters is possible. The clusters are investigated via IR photodissociation spectroscopy in the region of OH- and CH-stretching vibrations. The results are compared with theoretical data obtained from DFT calculations. Both frequency shifts and structural changes according to cluster size and composition are identified and discussed in detail, also with respect to cooperative effects. Trimeric metal clusters with an uneven number of nickel atoms show evidence for C-O cleavage of the ethanol molecule. This result is elucidated by further calculations concerning the reactivity, charge and energetic distributions.

Effects of Low-Level Laser Therapy and Purified Natural Latex (Hevea brasiliensis) Protein on Injured Sciatic Nerve in Rodents: Morpho-Functional Analysis.

The present study analyzed the effects of low-level laser therapy (LLLT) and the purified natural latex protein (Hevea brasiliensis, F1 protein) on the morpho-function of sciatic nerve crush injuries in rats. One-hundred and eight male Wistar rats were randomly allocated to six groups (n = 18): 1. Control; 2. Exposed (nerve exposed); 3. Injury (injured nerve without treatment); 4. LLLT (injured nerve irradiated with LLLT (15 J/cm2, 780 nm)); 5. F1 (injured nerve treated with F1 protein (0.1%)); and 6. LLLT + F1 (injured nerve treated with LLLT and F1). On the 1st, 7th, 14th, and 56th days after injury, a functional sensory analysis of mechanical allodynia and mechanical hyperalgesia and a motor analysis of grip strength and gait were performed. After 3, 15, and 57 days, the animals were euthanized for morphometric/ultrastructural analyses. The treatments applied revealed improvements in morphometric/ultrastructural parameters compared to the injured group. Sensory analyses suggested that the improvements observed were associated with time progression and not influenced by the treatments. Motor analyses revealed significant improvements in grip strength from the 7th day in the LLLT group and in gait from the 56th day in all treated groups. We concluded that even though the morphological analyses showed improvements with the treatments, they did not influence sensory recovery, and LLLT improved motor recovery.

Biological Properties of Dental Pulp Stem Cells Isolated from Inflamed and Healthy Pulp and Cultured in an Inflammatory Microenvironment.

INTRODUCTION: The aim of this study was to assess whether the biological characteristics of dental pulp stem cells (DPSCs), such as viability, adhesion to dentin, mineralization, and release of immunomodulatory cytokines, are affected by the inflammatory status of the donor tissue and/or the sustained inflammatory environment. METHODS: DPSCs were isolated from pulps from 3 caries-free teeth (healthy or hDPSCs), and from 3 teeth with irreversible pulpitis or deep caries (unhealthy DPSCs or uDPSCs). The cells were cultured in odontogenic and osteogenic media with or without lipopolysaccharides. Viability was analyzed by MTT assay at days 1, 3, 5, and 7; adhesion to dentin was evaluated through an environmental scanning electron microscope after 48 hours and through MTT assay; mineralization was analyzed with alizarin red staining after 21 days; and the release of proinflammatory (interleukin 6) and immunosuppressive cytokines (interleukin 10) was measured with the enzyme-linked immunosorbent assay after 24 hours and 7 days. RESULTS: The inflammatory status of the pulp significantly reduced the viability and mineralization capacity of the DPSCs, although it did not affect the adhesion capacity to dentin or the secretion of the proinflammatory interleukin. The inflammatory microenvironment (lipopolysaccharide) only had a significant impact on the secretion of interleukin 6, which was augmented after 7 days. CONCLUSIONS: The inflammatory status of the dental pulp should be taken into account when the use of DPSCs is intended either for research and/or for application in reparative or regenerative therapies.

Relación entre la cuenta de Twitter @ascolcirugia y las publicaciones de la Revista Colombiana de Cirugía durante la pandemia / Relationship between the Twitter account @ascolcirugia and the publications of the Colombian Journal of Surgery during the pandemic

Introducción. Indicadores alternativos basados en la web 2.0 han tomado importancia para medir el impacto de la producción científica. Previamente se han demostrado correlaciones positivas entre indicadores tradicionales y alternativos. El objetivo de este trabajo fue evaluar la relación de estos indicadores en el campo de la cirugía de nuestro país.Métodos. Análisis retrospectivo de las publicaciones de la Revista Colombiana de Cirugía y "tweets" de la cuenta @ascolcirugia entre marzo 2020 y julio 2021. Se evaluaron comparativamente los artículos con y sin publicación en la cuenta @ascolcirugia. Se determinó la correlación entre indicadores alternativos e indicadores tradicionales de las publicaciones de la revista. Resultados. En total se revisaron 149 artículos y 780 "tweets"; tan sólo el 13,4 % (n=20) de los artículos tuvieron visibilidad en la cuenta @ascolcirugia, con una mediana de 2 "tweets" (RIQ 1-2) por artículo, siendo la mayoría de estos sobre temas de COVID-19 (85 % vs 10 %; p<0,001). Los artículos publicados en @ascolcirugia tuvieron una mayor mediana de descargas (220 vs 116; p<0,001) y citaciones (3,5 vs 0; p<0,001) en comparación con los que no fueron publicados.Conclusión. El uso de las redes sociales tiene un efecto positivo en el número de lectores de la Revista Colombiana de Cirugía y el impacto académico de los autores. Aunque existe una buena correlación entre indicadores alternativos y tradicionales en el contexto nacional, la proporción de artículos de la Revista Colombiana de Cirugía publicados en la cuenta @ascolcirugia es baja.

Introduction. Alternative indicators based on web 2.0 have gained great relevance to measure the impact of scientific production. Positive correlations between traditional and alternative indicators have previously been shown. The objective of our article is to evaluate the relationship of these indicators in the field of surgery in our country.Methods. Retrospective analysis of the publications of the Colombian Journal of Surgery and tweets of the Twitter account (@ascolcirugia) during March 2020 and July 2021. Articles with and without tweets in the account @ascolcirugia were comparatively evaluated. The correlation between alternative indicators and traditional indicators of the journal's publications was determined. Results. A total of 149 articles and 780 tweets were reviewed; only 13.4% (n=20) of the articles had visibility at the @ascolcirugia account, with a median of 2 tweets (RIQ 1-2) per article, most of which were on COVID-19 issues (85% vs 10%; p<0.001). The articles published at the @ascolcirugia account had a higher median number of downloads (220 vs 116; p<0.001) and citations (3.5 vs 0; p<0.001) compared to the articles that were not published. Conclusions. The use of social media has a positive effect on the number of readers of the Colombian Journal of Surgery and the academic impact of the authors. Although there is a good correlation between alternative and traditional indicators, in the national context, the proportion of articles of the Colombian Journal of Surgery published at the @ascolcirugia account is low

Comparative study of fertility parameters in vitrified human spermatozoa in the presence or absence of EmbryORP® : A novel antioxidant.

The cryopreservation of spermatozoa has the main purpose of preserving male fertility. However, current preservation techniques have shown to produce lesions in the structure and alter sperm functions, probably due to the production of reactive oxygen species (ROS) during cryopreservation. To overcome the damage provoked by ROS, we introduced a novel antioxidant called EmbryORP® in a vitrification protocol and compared eight fertility parameters: motility, viability, morphology, concentration, the semen pH, the oxidation-reduction potential (ORP), the spontaneous acrosomal reaction (AR) and the mitochondrial membrane potential (MMP), in the presence or absence of EmbryORP® . We analysed 20 samples from healthy human sperm donors and observed that the antioxidant significantly decreased the semen pH as well as the MMP and the ORP affecting the balance of ROS. The antioxidant also lowered the motility and viability of the cells, but preserved the acrosome and sperm morphology in general. We concluded that EmbryORP® lowered the ORP, but to a suboptimal level that may be harmful to spermatozoa. Despite these results, our work opens new perspectives on how to improve cryopreservation media. Therefore, we recommend exploring the EmbryORP® potential benefit by reducing its concentration or changing the exposure time during the cryopreservation protocol.

Subchronic N-acetylcysteine Treatment Decreases Brain Kynurenic Acid Levels and Improves Cognitive Performance in Mice.

The tryptophan (Trp) metabolite kynurenic acid (KYNA) is an α7-nicotinic and N-methyl-d-aspartate receptor antagonist. Elevated brain KYNA levels are commonly seen in psychiatric disorders and neurodegenerative diseases and may be related to cognitive impairments. Recently, we showed that N-acetylcysteine (NAC) inhibits kynurenine aminotransferase II (KAT II), KYNA's key biosynthetic enzyme, and reduces KYNA neosynthesis in rats in vivo. In this study, we examined if repeated systemic administration of NAC influences brain KYNA and cognitive performance in mice. Animals received NAC (100 mg/kg, i.p.) daily for 7 days. Redox markers, KYNA levels, and KAT II activity were determined in the brain. We also assessed the effect of repeated NAC treatment on Trp catabolism using brain tissue slices ex vivo. Finally, learning and memory was evaluated with and without an acute challenge with KYNA's bioprecursor L-kynurenine (Kyn; 100 mg/kg). Subchronic NAC administration protected against an acute pro-oxidant challenge, decreased KYNA levels, and lowered KAT II activity and improved memory both under basal conditions and after acute Kyn treatment. In tissue slices from these mice, KYNA neosynthesis from Trp or Kyn was reduced. Together, our data indicate that prolonged treatment with NAC may enhance memory at least in part by reducing brain KYNA levels.

A combination of taurine and caffeine maintains sperm quality in equine semen during chilled storage.

OBJECTIVE: The objective of this study was to evaluate the effects of caffeine and taurine on the motility and viability of chilled equine semen. MATERIALS AND METHODS: A total of 12 ejaculates were collected from three mature stallions with proven fertility during the breeding season. The gel-free spermatic fraction of each ejaculate was divided into two aliquots and diluted with a semen extender (either INRA 96® or BotuSemen Gold®). The aliquots were then split and assigned to one of the six treatment groups: control (no supplement), caffeine (2 and 4 mM), taurine (25 and 50 mM), and a combination of caffeine (2 mM) plus taurine (25 mM). Samples were stored at 4°C and analyzed at different time points (0, 24, 48, 72, and 96 h) to evaluate total (TMOT) and progressive (PMOT) motility and viability by computer-assisted sperm analysis. RESULTS: Regardless of the extender, PMOT and TMOT decreased over time. However, compared with the control, the treatment with 4 mM caffeine significantly mitigated the decrease in PMOT at 72 h. Additionally, semen treated with a combination of caffeine plus taurine maintained a significantly higher PMOT at 96 h, with improved viability at all time points. CONCLUSIONS: The combination of caffeine plus taurine helps maintain chilled equine semen viability and progressive motility up to 96 h independently of the extender used.

Structure guided development of potent piperazine-derived hydroxamic acid inhibitors targeting falcilysin.

The protozoan parasite Plasmodium falciparum causes the most severe form of human malaria and is estimated to kill 400,000 people a year. The parasite infects and replicates in host red blood cells (RBCs), where it expresses an array of proteases to carry out multiple essential processes. We are investigating the function of falcilysin (FLN), a protease known to be required for parasite development in the RBC. We previously developed a piperazine-based hydroxamic acid scaffold to generate the first inhibitors of FLN, and the current study reports the optimization of the lead compound from that series. A range of substituents were tested at the N1 and N4 positions of the piperazine core, and inhibitors with significantly improved potency against purified FLN and cultured P. falciparum were identified. Computational studies were also performed to understand the mode of binding for these compounds, and predicted a binding model consistent with the biochemical data and the distinctive SAR observed at both the N1 and N4 positions.

Time-Lapse Flow Cytometry: A Robust Tool to Assess Physiological Parameters Related to the Fertilizing Capability of Human Sperm.

Plasma membrane (PM) hyperpolarization, increased intracellular pH (pHi), and changes in intracellular calcium concentration ([Ca2+]i) are physiological events that occur during human sperm capacitation. These parameters are potential predictors of successful outcomes for men undergoing artificial reproduction techniques (ARTs), but methods currently available for their determination pose various technical challenges and limitations. Here, we developed a novel strategy employing time-lapse flow cytometry (TLFC) to determine capacitation-related membrane potential (Em) and pHi changes, and progesterone-induced [Ca2+]i increases. Our results show that TLFC is a robust method to measure absolute Em and pHi values and to qualitatively evaluate [Ca2+]i changes. To support the usefulness of our methodology, we used sperm from two types of normozoospermic donors: known paternity (subjects with self-reported paternity) and no-known paternity (subjects without self-reported paternity and no known fertility problems). We found relevant differences between them. The incidences of membrane hyperpolarization, pHi alkalinization, and increased [Ca2+]i were consistently high among known paternity samples (100%, 100%, and 86%, respectively), while they varied widely among no-known paternity samples (44%, 17%, and 45%, respectively). Our results indicate that TLFC is a powerful tool to analyze key physiological parameters of human sperm, which pending clinical validation, could potentially be employed as fertility predictors.

The masked seducers: Lek courtship behavior in the wrinkle-faced bat Centurio senex (Phyllostomidae).

Centurio senex is an iconic bat characterized by a facial morphology deviating far from all other New World Leaf Nosed Bats (Phyllostomidae). The species has a bizarrely wrinkled face and lacks the characteristic nose leaf. Throughout its distribution from Mexico to Northern South America the species is most of the time rarely captured and only scarce information on its behavior and natural history is available. Centurio senex is frugivorous and one of the few bats documented to consume also hard seeds. Interestingly, the species shows a distinct sexual dimorphism: Adult males have more pronounced facial wrinkles than females and a fold of skin under the chin that can be raised in style of a face mask. We report the first observations on echolocation and mating behavior of Centurio senex, including synchronized audio and video recordings from an aggregation of males in Costa Rica. Over a period of 6 weeks we located a total of 53 perches, where during the first half of the night males were hanging with raised facial masks at a mean height of 2.35 m. Most of the time, the males moved just their wing tips, and spontaneously vocalized in the ultrasound range. Approaches of other individuals resulted in the perching male beating its wings and emitting a very loud, low frequency whistling call. Following such an encounter we recorded a copulation event. The observed aggregation of adult C. senex males is consistent with lek courtship, a behavior described from only few other bat species.

Kynurenine Pathway as a New Target of Cognitive Impairment Induced by Lead Toxicity During the Lactation.

The immature brain is especially vulnerable to lead (Pb2+) toxicity, which is considered an environmental neurotoxin. Pb2+ exposure during development compromises the cognitive and behavioral attributes which persist even later in adulthood, but the mechanisms involved in this effect are still unknown. On the other hand, the kynurenine pathway metabolites are modulators of different receptors and neurotransmitters related to cognition; specifically, high kynurenic acid levels has been involved with cognitive impairment, including deficits in spatial working memory and attention process. The aim of this study was to evaluate the relationship between the neurocognitive impairment induced by Pb2+ toxicity and the kynurenine pathway. The dams were divided in control group and Pb2+ group, which were given tap water or 500 ppm of lead acetate in drinking water ad libitum, respectively, from 0 to 23 postnatal day (PND). The poison was withdrawn, and tap water was given until 60 PND of the progeny. The locomotor activity in open field, redox environment, cellular function, kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) levels as well as kynurenine aminotransferase (KAT) and kynurenine monooxygenase (KMO) activities were evaluated at both 23 and 60 PND. Additionally, learning and memory through buried food location test and expression of KAT and KMO, and cellular damage were evaluated at 60 PND. Pb2+ group showed redox environment alterations, cellular dysfunction and KYNA and 3-HK levels increased. No changes were observed in KAT activity. KMO activity increased at 23 PND and decreased at 60 PND. No changes in KAT and KMO expression in control and Pb2+ group were observed, however the number of positive cells expressing KMO and KAT increased in relation to control, which correlated with the loss of neuronal population. Cognitive impairment was observed in Pb2+ group which was correlated with KYNA levels. These results suggest that the increase in KYNA levels could be a mechanism by which Pb2+ induces cognitive impairment in adult mice, hence the modulation of kynurenine pathway represents a potential target to improve behavioural alterations produced by this environmental toxin.

Cross-Cultural Adaptation of the Children's Emotion Regulation Processes Survey (CERP) in Chilean Preschoolers / Adaptação Transcultural do Questionário de Processos de Regulação Emocional (CERP) em Pré-Escolares Chilenos / Adaptación Transcultural del Cuestionario de Procesos de Regulación Emocional (CERP) en una Muestra de Preescolares Chilenos

Abstract Emotion regulation is an important aspect for the adaptation of human beings that influences their development and mental health. In actuality, it is an important challenge to have culturally valid instruments that allow to evaluate this construct. In this study, an analysis of the psychometric properties of the Children's Emotion Regulation Processes Survey (CERP) in a sample of Chilean preschoolers is presented. CERP is a third-party report questionnaire that assesses the strategies of emotion regulation in children, providing a vision based on development. The instrument was applied to mothers and fathers of 483 children, between the ages of 4 and 6 that attended preschool. Factorial structure, internal consistency and the relation with the Child Behavior Checklist (CBCL) as indicator of convergent validity was analyzed. The results showed a four factor structure, coherent with the empirical evidence. Also, all of the factors presented adequate reliability indexes and correlation with the internalization and externalization scales of CBCL. It is concluded that CERP exhibits positive reliability and validity indicators to be used in this population.

Resumo A regulação emocional é um aspecto de relevância para a adaptação dos indivíduos que influencia em seu desenvolvimento e saúde mental. Na atualidade, um desafio importante é contar com instrumentos válidos culturalmente que permitam avaliar este constructo. Neste estudo se apresenta a análise das propriedades psicométricas do Questionário de Processos de Regulação Emocional Infantil (CERP) em uma amostra de pré-escolares chilenos. O CERP é um questionário de relatórios de terceiros que avaliam estratégias de regulação emocional em crianças, entregando uma visão baseada no desenvolvimento. O instrumento foi aplicado a pais e mães de 483 crianças, entre 4 e 6 anos que cursavam a educação pré-escolar. Foi analisada a estrutura fatorial, consistência interna e o relacionamento com o Inventario de Condutas Infantis (CBCL) como indicador de validade convergente. Os resultados evidenciaram uma estrutura de quatro fatores, coerentes com a evidencia empírica. Além disso, todos os fatores apresentaram índices adequados de confiabilidade e correlações com as escalas de internalização e terceirização do CBCL. Se conclui que o CERP mostra indicadores de confiabilidade e validez positivos para serem usados nesta população.

Resumen La regulación emocional es un aspecto de relevancia para la adaptación de los individuos que influye en su desarrollo y salud mental. Actualmente, es un desafío contar con instrumentos válidos culturalmente para evaluar este constructo. En este estudio, se presenta el análisis de las propiedades psicométricas del Cuestionario de Procesos de Regulación Emocional Infantil (CERP) en una muestra de preescolares chilenos. El CERP es un cuestionario de reporte de terceros que evalúa las estrategias de regulación emocional en niños/as, entregando una visión basada en el desarrollo. Se aplicó el instrumento a padres y madres de 483 niños/as de edades entre 4 y 6 años que cursaban educación preescolar. Se analizó la estructura factorial, consistencia interna y relación con el Inventario de Conductas Infantiles (CBCL) como indicador de validez convergente. Los resultados evidenciaron una estructura de cuatro factores, coherentes con la evidencia empírica. Además, todos los factores presentaron adecuados índices de confiabilidad y correlaciones con las escalas de internalización y externalización del CBCL. Se concluye que el CERP muestra indicadores de confiabilidad y validez positivos para ser usado en esta población.