Neonatal overfeeding alters the functioning of the mesolimbic dopaminergic circuitry involving changes in DNA methylation and effects on feeding behavior.

Mesolimbic dopaminergic circuit is essential for food reward and motivational behaviors and can contribute to weight gain and obesity. Litter reduction is a classical model for studying the effects of neonatal overfeeding and overweight. Litters of Wistar rats were reduced to 4 pups/dam for small litter (SL) and 10 pups/dam for normal litter at postnatal day (PND) 4. Immediately after performing the feeding behavior tests, the animals were sacrificed in PND21 and PND90. The ventral tegmental area (VTA), Nucleus Accumbens Core (NAcC) and Shell (NAcSh) were isolated from frozen brain sections using the Palkovits micropunch technique. RNA and DNA were extracted from these areas, gene expression was measured by RT-qPCR and DNA methylation levels were measured by MSRM-qPCR technique. SL-PND21 animals presented increased expression levels of Tyrosine Hydroxylase and Dopamine Receptor D2 in VTA, decreased expression levels of dopamine active transporter (DAT) in VTA, and higher expression levels of DAT in NAcC. On the other hand, SL-PND90 animals showed decreased expression levels of Dopamine Receptor D1 and higher expression of DAT in NAcSh. These animals also evidenced impaired sensory-specific satiety. In addition, altered promoter methylation was observed at weaning, and remained in adulthood. This work demonstrates that neonatal overfeeding induces disruptions in the mesolimbic dopaminergic circuitry and causes alterations in feeding behavior from weaning to adulthood, suggesting that the neonatal period is critical for the normal development of dopaminergic circuit that impact on feeding behavior.

Traditional medicine in Incahuasi: An ethnobotanical study.

Introduction: Understanding the use of medicinal plants as herbal medicines is considered essential for the survival and continuity of humanity. Since ancient times, the origin and development of natural and traditional medicine have been intrinsically linked to humanity struggle for survival. Nowadays, ethnobotanical studies are employed as a tool for the preservation and conservation not only of taxonomic biodiversity but also of cultural biodiversity. Methodology: A descriptive research with a quantitative, non-experimental cross-sectional design was carried out. The study was conducted in six Quechua-speaking communities in the district of Incahuasi (3,000 meters above sea level), selected for convenience considering factors such as altitude, accessibility, and proximity to the city. A questionnaire was administered to 32 residents from the communities, who shared their knowledge about medicinal plants, providing relevant information about them. The gender of the participants was considered because men and women use traditional medicine and the knowledge of them is transmitted from parents to children. Results: During the study, a total of 46 medicinal species were recorded, belonging to 42 genera and 22 botanical families. The most representative medicinal families used by the informants of the communities were Asteraceae (30.4%) and Lamiaceae (15.2%). It is also worth mentioning the genera Salvia and Baccharis, with three and two species respectively, which are commonly used to treat various ailments and diseases. Conclusions: Ethnobotanical information was collected on the medicinal plants used by the community members of the selected communities in Incahuasi, and the corresponding data were recorded. A total of 46 plants were collected, with the majority belonging to the Asteraceae and Lamiaceae families.

Epigenetic disruption of placental genes by chronic maternal cafeteria diet in rats.

Maternal diet has impact on reproduction, fetal development and offspring behavior, although molecular mechanisms remained unknown. Our aims were to assess (1) the effects of a cafeteria (CAF) diet (western diet habits) on female reproductive performance, fetal and placental parameters on gestational day 21 and litter size and pup weight at birth; and (2) placental messenger RNA (mRNA) expression and epigenetic regulation of Insulin-Like Growth Factor (Igf) and Vascular Endothelial Growth Factor (Vegf) and their receptors. Female Wistar rats were fed with control or CAF diet from weaning until parturition. At week 14 after diets started, females were mated and half of the animals were euthanized on gestational day 21 to evaluate reproductive parameters including the pregnancy rate, number of corpora lutea, implantation sites and resorption sites. Moreover, fetal weight and length, placental weight, and placental index were recorded. Placentas were collected for mRNA quantification and DNA methylation analysis. The remaining animals were allowed to give birth and the number and weight of the pups were evaluated. CAF diet did not affect reproductive performance or fetal weight and length. However, CAF-fed animals showed a decrease in placental weight and index and the pups exhibited a low birth weight. Additionally, we found an upregulation of Igf2 and a down regulation of Vegf placental mRNA expression in CAF dams, associated with methylation status changes of their promoters. We conclude that female chronic CAF diet consumption impairs feto-placental development and could be explained by an epigenetic disruption of Igf and Vegf systems.

Steroidogenic enzymes in the hippocampus: Transcriptional regulation aspects.

Neurosteroids are steroids synthesized de novo from cholesterol in brain regions, and regulate processes associated with the development and functioning of the nervous system. Enzymes and proteins involved in the synthesis of these steroids have been detected in several brain regions, including hippocampus, hypothalamus, and cerebral cortex. Hippocampus has long been associated with learning and memory functions, while the loss of its functionality has been linked to neurodegenerative pathologies. In this sense, neurosteroids are critical for the maintenance of hippocampal functions and neuroprotective effects. Moreover, several factors have been shown to deregulate expression of steroidogenic enzymes in the rodent brain, including aging, enrichment experiences, diet habits, drug/alcohol consumption, hormone fluctuations, neurodegenerative processes and other diseases. These transcriptional deregulations are mediated mainly by transcription factors and epigenetic mechanisms. An epigenetic modification of chromatin involves changes in bases and associated proteins in the absence of changes in the DNA sequence. One of the most well-studied mechanisms related to gene silencing is DNA methylation, which involves a reversible addition of methyl groups in a cytosine base. Importantly, these epigenetic marks could be maintained over time and could be transmitted transgenerationally. The aim of this chapter is to present the most relevant steroidogenic enzymes described in rodent hippocampus; to discuss about their transcriptional regulation under different conditions; to show the main gene control regions and to propose DNA methylation as an epigenetic mechanism through which the expression of these enzymes could be controlled.

Burnout and anxiety levels in human medicine teachers, COVID-19 context.

Introduction: In the COVID-19 context, university teachers have had to face the most complex educational demands, psychosocial risks, and the anxiety of responding to limitations in terms of connectivity and fulfillment of academic objectives . To identify the levels of Burnout and anxiety in the COVID-19 context and determine how these levels are manifested in the participating teachers. Methods: This was an analytical non-experimental, cross-sectional study. The population was 150 teachers of the Human Medicine Program of the University of San Martín de Porres, Chiclayo, Peru, and the sample was 66 teachers. The survey consisted of three sections: 1. Informed consent, 2. Maslach's Burnout Inventory, 3. Beck's Anxiety Inventory. Data processing was performed using the SPSS V.27 statistical software and all citations and bibliographical references were processed using Mendeley Desktop 1.19.8. Results: In the variable burnout syndrome, 25% of the participants were in the high level downwards; they present anxiety in 30.30% of the total. It was found that 50% of teachers presented mild to moderate anxiety. Conclusions: the largest number of teachers surveyed present anxiety due to burnout syndrome in the COVID-19 context. Finally, it is found that there is a correlation between anxiety and the sociodemographic variables sex, age, and marital status.

Medicinal properties of Morus alba for the control of type 2 diabetes mellitus: a systematic review.

Background: The objective of this review was to evaluate the medicinal potential of Morus alba leaves on the control of type 2 diabetes mellitus (DM2). The research question was: what is the therapeutic potential of Morus alba leaves for the control of DM2? Methods: This systematic review was based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The included studies were extracted from Scopus, Pubmed, ScienceDirect, Scielo, and Google Scholar; January 2015 to July 2021. Key search terms were MeSH and DeCS: Morus alba, mulberry, hypoglycemic agent. The inclusion criteria were: studies in rats administered Morus alba leaf extracts; studies that included the dimensions of lipidemia and glycemia; studies that included indicators such as fasting glucose, postprandial glucose, glycosylated hemoglobin, triglycerides, low-density lipoproteins, total cholesterol, and insulin resistance. Exclusion criteria: studies in which Morus alba leaves were administered with other plants; studies with other parts of the Morus alba plant; proteomic studies, cancer, duplicate studies, in vitro studies, and evaluation of included studies. All included investigations were evaluated for biases. Results: Of 253 studies found, 29 were included. The extracts of Morus alba leaves at the phytochemical level improve glucose uptake. Chlorogenic acid, isoquercitrin, and quercitrin, present in the leaves of Morus alba, have hypoglycemic properties and an ameliorating effect on diabetic nephropathy. This leaf has pharmacological effects such as glucose absorption, insulin secretion production, antioxidant and anti-inflammatory agent, antihyperglycemic and antihyperlipidemic activities, and obesity management. Conclusions:Morus alba leaves have pharmacological effects on DM2 that include glucose absorption, production of insulin secretion, antioxidant agent, antihyperglycemic and antihyperlipidemic activities, and obesity control. Beyond these results, there is a lack of studies on the potential and synergistic effects of Morus alba leaves' components, limiting the possibility of a more effective therapy using the plant's leaves.

Costo beneficio de acetaminofén en tableta en establecimientos farmacéuticos de Lima / Cost benefit of acetaminophen in tablet in pharmaceutical establishments of Lima

Introducción: La economía de los medicamentos se puede considerar como el estudio y cálculo económico detallados del medicamento, que ayuda a satisfacer las necesidades del paciente según costo, beneficio y eficacia de dicho medicamento. Objetivo: El objetivo de la investigación fue evaluar si la valoración económica de la tableta de acetaminofén 500 mg. permitirá conocer el beneficio en el costo del fármaco en los establecimientos farmacéuticos de Lima. Métodos: La investigación presenta un diseño no experimental, transversal, descriptivo y analítico. Población: 25 trabajadores de la DIGEMID con conocimientos de farmacoeconomía; muestra: 100 por ciento de la población. Para la evaluación se utilizó un cuestionario de escala Likert, basado en las dos variables cuantitativas: Valoración económica y Coste-beneficio. El tratamiento estadístico se realizó con el programa SPSS v.25. Traducción realizada con la versión gratuita del traductor www.DeepL.com/Translator Resultados: De un total de 44 presentaciones de tabletas de acetaminofén vendidas en 41 distritos de Lima, se obtuvieron siete presentaciones que ofrecen el producto a un precio elevado, siendo estas no beneficiosas en el 15,9 por ciento y se encontraron 37 establecimientos que ofrecen el medicamento a un precio medio beneficioso (84,1 por ciento). Conclusiones: La farmacoeconomía aplicada al medicamento acetaminofén presentación tableta 500 mg permitió conocer que dicho producto tiene un costo de bajo a moderado, por lo que es asequible a la población de bajos recursos. Asimismo, la evaluación económica efectuada permitirá la toma de decisiones del consumidor al momento de la compra(AU)

Introduction: The economics of medicines can be considered as the detailed economic study and calculation of the treatment, which helps to satisfy the needs of the patient according to the cost, benefit, and efficacy of said medicine. Objective: The objective of the research was to evaluate if the economic valuation of the acetaminophen 500 mg. tablet will allow to know the benefit in the cost of the drug in pharmaceutical establishments in Lima. Methods: The research presents a non-experimental, cross-sectional, descriptive, and analytical design. Population: 25 DIGEMID workers with knowledge of pharmacoeconomics; sample: 100 percent of the population. A Likert scale questionnaire was used for the evaluation, based on the two quantitative variables: Economic valuation and Cost-benefit. Statistical processing was carried out using the SPSS v.25 program. Results: From a total of 44 presentations of acetaminophen tablets sold in 41 districts of Lima, seven presentations have been obtained that offer the product at a high price, these being not beneficial and reaching 15.9 percent, 37 establishments were found They offer the drug at a helpful average price reaching 84.1 percent. Conclusions: The pharmacoeconomics applied to the drug acetaminophen 500 mg tablet presentation allowed us to know that this product has a low to moderate cost, making it affordable to the low-income population. Likewise, the economic evaluation carried out will allow decision-making at the time of purchase, which will enable the people to identify the price(AU)

Epigenetic Changes Associated With Exposure to Glyphosate-Based Herbicides in Mammals.

Glyphosate is a phosphonomethyl amino acid derivative present in a number of non-selective and systemic herbicides. During the last years the use of glyphosate-based herbicide (GBH) has been increasing exponentially around the world, including Argentina. This fact added to the detection of glyphosate, and its main metabolite, amino methylphosphonic acid (AMPA), in environmental matrices such as soil, sediments, and food, has generated great concern about its risks for humans, animals, and environment. During the last years, there were controversy and intense debate regarding the toxicological effects of these compounds associated with the endocrine system, cancer, reproduction, and development. The mechanisms of action of GBH and their metabolites are still under investigation, although recent findings have shown that they could comprise epigenetic modifications. These are reversible mechanisms linked to tissue-specific silencing of gene expression, genomic imprinting, and tumor growth. Particularly, glyphosate, GBH, and AMPA have been reported to produce changes in global DNA methylation, methylation of specific genes, histone modification, and differential expression of non-coding RNAs in human cells and rodents. Importantly, the epigenome could be heritable and could lead to disease long after the exposure has ended. This mini-review summarizes the epigenetic changes produced by glyphosate, GBHs, and AMPA in humans and rodents and proposes it as a potential mechanism of action through which these chemical compounds could alter body functions.

Temporary effects of neonatal overfeeding on homeostatic control of food intake involve alterations in POMC promoter methylation in male rats.

A small litter (SL) model was used to determine how neonatal overfeeding affects the homeostatic control of food intake in male rats at weaning and postnatal day (PND) 90. At PND4, litters were reduced to small (4 pups/dam) or normal (10 pups/dam) litters. At weaning, SL rats showed higher body weight and characteristic features of the metabolic syndrome. Gene expression of pro-opiomelanocortin (POMC), cocaine and amphetamine regulated transcript, neuropeptide Y (NPY) and leptin and ghrelin (GHSR) receptors were increased and POMC promoter was hypomethylated in arcuate nucleus, indicating that the early development of obesity may involve the GHSR/NPY system and changes in POMC methylation state. At PND90, body weight, metabolic parameters and gene expression were restored; however, POMC methylation state remained altered. This work provides insight into the effects of neonatal overfeeding, showing the importance of developmental plasticity in restoring early changes in central pathways involved in metabolic programming.

Cafeteria diet induces progressive changes in hypothalamic mechanisms involved in food intake control at different feeding periods in female rats.

We studied the effects of cafeteria diet (CAF) intake from weaning on mRNA levels and DNA methylation state of feeding-related neuropeptides and hormone receptors in individual hypothalamic nuclei at different feeding periods. Four weeks of CAF (short-term) increased energy intake and adiposity, without affecting neuropeptides' expression. Eleven weeks of CAF (medium-term) increased energy intake, adiposity, leptinemia, and body weight, with an orexigenic response of the lateral hypothalamus, paraventricular and ventromedial nuclei, given by upregulation of Orexins, AgRP, and NPY opposed by an anorectic signal of the arcuate nucleus, which displayed a higher POMC expression. The changes in neuropeptidic mRNA levels were related to epigenetic modifications in their promoter regions. Metabolic and molecular changes were intensified after 20 weeks of diet (long-term). The alterations in these hypothalamic brain nuclei could add information about their differential role in food intake control, and how their action is disrupted during the development of obesity.

The impact of sensory and motor enrichment on the epigenetic control of steroidogenic-related genes in rat hippocampus.

In the present study, we analyzed the effects of a short-term environmental enrichment on the mRNA expression and DNA methylation of steroidogenic enzymes in the hippocampus. Thus, young adult (80-day-old) and middle-aged (350-day-old) Wistar female rats were exposed to sensory (SE) or motor (ME) enrichment during 10 days and compared to animals housed under standard conditions. SE was provided by an assortment of objects that included plastic tubes and toys; for ME, rodent wheels were provided. In young adult animals, SE and ME increased the mRNA expression of cytochrome P450 17α-hydroxylase/c17,20-lyase, steroid 5α-reductase type 1 (5αR-1) and 3α-hydroxysteroid dehydrogenase and decreased the methylation levels of 5αR-1 gene. In middle-aged rats, ME and SE upregulated the gene expression of aldosterone synthase and decreased the methylation state of its promoter. These results propose that SE and ME differentially regulate the transcription of neurosteroidogenic enzymes through epigenetic mechanisms in young and aged rats.

Induction of uterine hyperplasia after cafeteria diet exposure.

Our aim was to evaluate whether chronic administration of CAF affects the uterus and induces the morphological and molecular changes associated with endometrial hyperplasia. Female Wistar rats exposed to CAF from weaning for 20 weeks displayed increased energy intake, body weight and fat depots, but did not develop metabolic syndrome. The adult uteri showed an increase in glandular volume fraction and stromal area. The epithelial proliferation rate and protein expression of oestrogen receptor alpha (ERα) were also increased. The CAF diet enhanced leptin serum levels and the long form of leptin receptor (Ob-Rb) mRNA expression in the uterus. No changes were detected in either insulin serum levels or those of insulin growth factor I (IGF-I) mRNA expression. However the levels of IGF-I receptor (IGF-IR) mRNA were lower in CAF-fed animals. Overall, the results indicate that our rat model of the CAF diet produces morphological and molecular changes associated with uterine hyperplasia and could predispose to endometrial carcinogenesis.

Cafeteria diet differentially alters the expression of feeding-related genes through DNA methylation mechanisms in individual hypothalamic nuclei.

We evaluated the effect of cafeteria diet (CAF) on the mRNA levels and DNA methylation state of feeding-related neuropeptides, and neurosteroidogenic enzymes in discrete hypothalamic nuclei. Besides, the expression of steroid hormone receptors was analyzed. Female rats fed with CAF from weaning increased their energy intake, body weight, and fat depots, but did not develop metabolic syndrome. The increase in energy intake was related to an orexigenic signal of paraventricular (PVN) and ventromedial (VMN) nuclei, given principally by upregulation of AgRP and NPY. This was mildly counteracted by the arcuate nucleus, with decreased AgRP expression and increased POMC and kisspeptin expression. CAF altered the transcription of neurosteroidogenic enzymes in PVN and VMN, and epigenetic mechanisms associated with differential promoter methylation were involved. The changes observed in the hypothalamic nuclei studied could add information about their differential role in food intake control and how their action is disrupted in obesity.

Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism.

The absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis. Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance. Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake.

Sexually dimorphic expression of receptor-alpha in the cerebral cortex of neonatal Caiman latirostris (Crocodylia: Alligatoridae).

In mammals, estrogens have been described as endocrine and paracrine modulators of neuronal differentiation and synapse formation. However, the functional role of circulating estrogens and the distribution of estrogen receptors (ERs) in the cerebral cortex of reptiles have not been clearly established. Caiman latirostris (C. latirostris) is a South American species that presents temperature-dependent sex determination (TSD). By using immunohistochemistry, we have studied the distribution of ERα in the cerebral cortex of neonatal caimans. We studied brain samples from ten-day-old TSD-females and TSD-males and from female caimans that were administered estradiol during embryonic development (hormone-dependent sex determination, HSD-females). ERα was detected in the medial (MC), dorsal (DC) and lateral (LC) cortices. ERα expression in the MC showed sex-associated differences, being significantly greater in TSD-females compared to TSD-males. Interestingly, the highest ERα expression in the MC was exhibited by HSD-females. In addition, the circulating levels of estradiol were significantly higher in females (both TSD and HSD) than in TSD-males. Double immunostaining showed that ERα is expressed by neural precursor cells (as detected by ERα/doublecortin or ERα/glial fibrillary acidic protein) and mature neurons (ERα/neuron-specific nuclear protein). Our results demonstrate that the expression of ERα in the neonatal caiman cortex is sexually dimorphic and is present in the early stages of neuronal differentiation.