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ABSTRACT University social responsibility is a set of actions that helps to promote the active participation of students in their university education, with ethical conduct to create a culture of social commitment based on values and academic quality. The main role of the university is to develop the functions of teaching, research and social responsibility; this allows creating a broader vision of the needs in the community, generating competent professionals and causing a positive impact (Palomino, Vázquez, Vicente, & Tomás, 2019). Objective: To identify the main authors of the subject from the systematic review of the literature, to point out the four axis that RSU has and the four university impacts. Materials and methods: This research is exploratory and documentary with a qualitative approach. The information sources used correspond to consultation pages, among which are: Google academic, and Lens.org. Likewise, inclusion and exclusion criteria were used to collect information and the results obtained were delimited after adding search conditions such as the year interval from 2017 to 2023. Another limitation is that they were only review articles and in any language. Results: The results obtained were 10 definitions of prominent authors which haves an impact on the fact that the University social responsibility has 8 dimensions among which are: Responsible Campus, Citizen Education, Social Knowledge Management, and Mutual Learning Communities for Development, Organizational, Educational, Cognitive and social. The four axis of the RSU are the basis of the organizations to be able to fulfill the mission that each university community pursues. Within the responsible campus, care is taken to ensure that environmental and sustainable care is met and students are taught to participate in it. , responsible citizen and professional training, deontology, which is the duty of people, this helps the university community to do things ethically and with good morals inside and outside universities, knowledge management is a of the main tasks of higher education institutions, social work, the reason for being of various organizations, thanks to which they can disseminate their knowledge and contribute to the development of community and group culture, and finally the need for The society of inclusion and communication between people occur within communities of mutual learning for development. The organizational impacts, within the RSU, impact people, management and sustainability. The educational impacts are related to the training of students (their ethics, their way of interpreting the world and the social role that corresponds to them) and involves all university processes (curriculum, central administration and knowledge management policies). Cognitive impacts are the dissemination of knowledge and social impacts are the relationship within and on the university campus, the treatment and participation of students; Students in the different branches offered. When reviewing and reading the different existing articles, it was observed that there is little information regarding the RSU, focusing on a chronology of the different authors from 2014 to date. Within the articles reviewed, it can be defined that RSU trains, teaches, supports, promotes, guides and organizes; involving the student community, teachers, administrative and managerial staff. The RSU transmits responsible knowledge, ethical principles and helps to train responsible citizen professionals. Conclusion: After studying the literary review, it can be mentioned that all the axis of the RSU must have the participation of the students and all the people who make up the university community in order to have a responsible university, both internally and externally, according to the different concepts that are mentioned of University Social Responsibility; In other words, it is a way to help the professional and civic training of all students, since this is part of what social responsibility seeks. It is mentioned that university students must get involved in real problems within their professional and civic training, since this helps to create links between learning and social responsibility and thus be able to promote human development, both ethically and morally, as that participation in the different projects that the same institution carries out in its activities will grow.Ramírez (2020),Quezada and Rodríguez (2019),Arauco and Apaza (2022),Évora (2017), agree that RSU is reflected in the existence of four axis for the socially responsible management of universities, so that the students are aware that everything that is done within the institution will be reflected outside of it. Complying with Social Responsibility in higher education is a transformation resource that promotes compliance with transparent practices and ethical conduct for sustainable development, generating social well-being on the university campus for the comprehensive and ideal training of its students. Currently, globalization leads to constant changes in organizations and forces them to be able to identify their challenges for the new trends that their environment requires. Therefore, globalization, competition, technology, social responsibility, knowledge and intangible assets demand serious modifications in their structures and strategies from companies.Niebles Nuñez et al. (2018)the universities have the important mission of equitably distributing knowledge and social information. That is why universities must assume the position of University Social Responsibility and analyze whether effective or null knowledge is being provided. The current era is characterized by its constant change, in social demands, in the role of traditional actors, in the situation at the regional and international level, in development approaches (Uribe et al., 2020). Addressing the issue of RSU requires articulating the various parts of the institution in an equitable and sustainable social promotion project, for the production and transmission of responsible knowledge and the training of equally responsible citizen professionals (Mosquera Tayupanta and Alba Granados, 2021; Peña y otros, 2017). There is a proposal for university social responsibility that provides a space for participation in the activities carried out and that are adapted to the new acquisition modalities for students, in addition to the fact that university social responsibility seeks not only to work on the axis of transformation within of the institution, but is also aimed at the entire society that is involved (Pedró, 2019). The university must promote the participation of its students in cultural, social, sports and environmental activities.
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BACKGROUND: ISG15 deficiency is a mixed syndrome of Mendelian susceptibility to mycobacterial infections (MSMD), a rare inherited condition characterized primarily by recurrent infections from low-virulence mycobacteria and monogenic type I interferonopathy. OBJECTIVE: To characterize the laboratory and molecular features of two patients from different families affected by the same ISG15 variant. METHODS: We began with clinical characterization and investigation, assessed IL-12/IFN-γ production, performed genetic characterization through WES and Sanger sequencing, conducted an in silico molecular analysis of the genetic ISG15 variant's protein impact, and utilized RNAseq for transcriptome analysis to understand pathway impacts on ISG15-deficient subjects from unrelated families. RESULTS: A mutation in the ISG15 gene was identified, affecting two patients treated in different hospitals and cities in Brazil (Fortaleza and Sao Paulo), who are also members of unrelated families. Both patients showed low IFN-γ production when stimulated with BCG or BCG + IL-12. ISG15 deficiency presented with two distinct clinical phenotypes: infectious and neurological. It was identified that both patients are homozygous for the variant (c.83 T > A). Furthermore, it was observed that the mutant protein p.L28Q results in an unstable protein with increased flexibility (ΔΔG: -2.400 kcal/mol). Transcriptome analysis revealed 1321 differentially expressed genes, with significant upregulation in interferon pathways, showing higher expression in patients compared to controls. CONCLUSION: This study describes the first reported cases in Brazil of two unrelated patients with the same ISG15 mutation c.83 T > A, exhibiting infectious features such as mycobacterial infections and systemic candidiasis, neurological findings, and skin lesions, without adverse reactions to the BCG vaccine. CLINICAL IMPLICATIONS: Reporting ISG15 gene mutations in Brazilian patients enhances understanding of genetic susceptibilities, guiding effective diagnostics and treatment. Identifying high-risk individuals aids clinical practices, genetic counseling, and influences public health policies. We have identified the first case in Brazil of the same ISG15 variant c.83 T > A that was identified in two unrelated patients with distinct clinical phenotypes, infectious and neurological.
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Citocinas , Mutación , Ubiquitinas , Humanos , Citocinas/metabolismo , Ubiquitinas/genética , Brasil , Mutación/genética , Masculino , Femenino , Linaje , Predisposición Genética a la Enfermedad , Interferón gamma/genética , Lactante , Infecciones por Mycobacterium/genética , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/etiología , Preescolar , Fenotipo , NiñoRESUMEN
Prior investigation shows that diabetic patients present hypothalamus-pituitary-adrenal (HPA) axis hyperactivity related to impaired negative feedback. This study investigates the effect of Captopril on the overproduction of adrenocorticotropic hormone (ACTH) and its precursor proopiomelanocortin (POMC) in the pituitary gland of male diabetic mice. Diabetes was induced by intravenous injection of alloxan into fasted Swiss-webster mice, and the animals were treated with Captopril for 14 consecutive days, starting 7 days post-diabetes induction. Plasma corticosterone levels were evaluated by ELISA, while pituitary gland expressions of angiotensin-II type 1 receptor (AT1), angiotensin-II type 2 receptor (AT2), ACTH, Bax, Bcl-2, KI-67, POMC, and glucocorticoid receptor (GR) were evaluated using immunohistochemistry or Western blot. Diabetic mice showed pituitary gland overexpression of AT1, without altering AT2 levels, which were sensitive to Captopril treatment. Furthermore, diabetic mice presented hypercortisolism, along with an increase in the number of corticotroph cells, POMC and ACTH expression, and number of proliferative cells, and a decrease of GR expression in the pituitary gland. In addition, treatment with Captopril reduced systemic corticosterone levels, corticotroph and proliferative cell numbers, and Bcl-2, POMC, and ACTH expression in the pituitary gland of diabetic mice, besides increasing the expression of Bax and GR. In conclusion, these findings show that Captopril is a promising therapy for treating complications associated with HPA axis hyperactivity in diabetic patients, in a mechanism probably related to the downregulation of POMC production in the pituitary gland and subsequent reduction of systemic corticosterone levels.
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Alzheimer's disease (AD) is a degenerative disease that causes a progressive decline in memory and thinking skills. Over the past few years, diverse studies have shown that there is no single cause of AD; instead, it has been reported that factors such as genetics, lifestyle, and environment contribute to the pathogenesis of the disease. In this sense, it has been shown that obesity during middle age is one of the most prominent modifiable risk factors for AD. Of the multiple potential mechanisms linking obesity and AD, the gut microbiota (GM) has gained increasing attention in recent years. However, the underlying mechanisms that connect the GM with the process of neurodegeneration remain unclear. Through this narrative review, we present a comprehensive understanding of how alterations in the GM of people with obesity may result in systemic inflammation and affect pathways related to the pathogenesis of AD. We conclude with an analysis of the relationship between GM and insulin resistance, a risk factor for AD that is highly prevalent in people with obesity. Understanding the crosstalk between obesity, GM, and the pathogenesis of AD will help to design new strategies aimed at preventing neurodegeneration.
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Enfermedad de Alzheimer , Microbioma Gastrointestinal , Obesidad , Enfermedad de Alzheimer/microbiología , Humanos , Microbioma Gastrointestinal/fisiología , Obesidad/microbiología , Obesidad/complicaciones , Resistencia a la Insulina/fisiología , Animales , Factores de Riesgo , Eje Cerebro-Intestino/fisiología , Inflamación/microbiologíaRESUMEN
Stress, unhealthy lifestyle, and sleep disturbance worsen cognitive function in mood disorders, prompting a rise in the development of integrative health approaches. The recent investigations in the gut-brain axis field highlight the strong interplay among microbiota, inflammation, and mental health. Thus, this study aimed to investigate a new nutraceutical formulation comprising prebiotics, minerals, and silymarin's impact on microbiota, inflammation, mood, and sleep quality. The study evaluated the LL1 + silymarin capsule supplementation over 180 days in overweight adults. We analyzed the fecal gut microbiota using partial 16S rRNA sequences, measured cytokine expression via CBA, collected anthropometric data, quality of life, and sleep questionnaire responses, and obtained plasma samples for metabolic and hormonal analysis at baseline (T0) and 180 days (T180) post-supplementation. Our findings revealed significant reshaping in gut microbiota composition at the phylum, genus, and species levels, especially in the butyrate-producer bacteria post-supplementation. These changes in gut microbiota were linked to enhancements in sleep quality, mood perception, cytokine expression, and anthropometric measures which microbiota-derived short-chain fatty acids might enhance. The supplementation tested in this study seems to be able to improve microbiota composition, reflecting anthropometrics and inflammation, as well as sleep quality and mood improvement.
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Afecto , Eje Cerebro-Intestino , Suplementos Dietéticos , Microbioma Gastrointestinal , Silimarina , Calidad del Sueño , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Proyectos Piloto , Afecto/efectos de los fármacos , Masculino , Femenino , Silimarina/farmacología , Adulto , Eje Cerebro-Intestino/efectos de los fármacos , Persona de Mediana Edad , Calidad de Vida , Heces/microbiología , Cápsulas , Citocinas/metabolismo , Citocinas/sangre , Sobrepeso , Prebióticos/administración & dosificación , ARN Ribosómico 16SRESUMEN
BACKGROUND: Depressive symptoms during perinatal significantly impact mothers and infants. Emerging evidence suggests a connection between gut microbiota and mood regulation. This study investigated whether depressive symptoms are associated with changes in the gut microbiota of women during the perinatal period. METHOD: A total of 34 pregnant women were screened for depression using the Edinburgh Postnatal Depression Scale (EPDS) and categorized based on symptom severity. Stool samples were collected during the third trimester and at two postpartum timepoints. All samples underwent 16S rRNA gene sequencing and Quantification of Short-Chain Fatty Acids (SCFA) using a gas chromatograph-mass spectrometer (GC-MS). RESULTS: No differences in SCFA concentrations were observed between groups (p>0.05). However, postpartum women with moderate to severe symptoms (MG group) had a significant increase in Enterobacteriaceae abundance compared to the mild and absent group (AL group) (p<0.05). The Bifidobacterium genus increased significantly in both groups over time (p<0.05). The MG group showed a reduction in depressive symptoms during psychiatric treatment (p<0.05). CONCLUSION: These findings suggest a link between gut microbiota and perinatal depressive symptoms. Further research is needed to understand the broader implications for maternal health through microbiome-targeted approaches.
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Diabetes is a complex disease, despite the availability of numerous treatments, its progression and complications can only be mitigated and managed to a certain extent. After the onset, diabetes cannot be reversed. Its global expansion makes it challenging for governments to control the considerable costs of treating people with diabetes. Many studies have been carried out by widely recognized pharmaceutical companies that are considering the development of new drugs for diabetic treatments. Diets, sedentary habits, and lifestyles that are currently prevalent have an enormous influence on the global spread of diabetes. The tools available to clinicians for therapy do not solve the problem. It is known that a patient, when diagnosed, would already have had diabetes for more than three years. Studies on diabetes signaling consider the effects of hyperglycemia but also highlight the roles of insulin receptor activation and resistance. Understanding the intricate signaling network and its interactions with hyperglycemiainduced pathways is crucial. In this context, the cyclic AMP/AMPK axis emerges as a promising therapeutic target for diabetes. However, there is a noticeable lack of literature exploring the metabolic network induced by hyperglycemia and its interconnected pathways. Therefore, investigating the cyclic cAMP/AMPK axis could provide valuable insights, given its complex connections with various metabolic pathways. This mini-review aims to delve into the metabolic signaling of the AMPK/cAMP axis in the context of diabetes, highlighting its metabolic interactions and potential implications.
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Background: The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Methods: Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. Results: The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. Conclusion: The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.
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Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Transcriptoma , Humanos , Neoplasias Pulmonares/microbiología , Neoplasias Pulmonares/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Biología Computacional , Pulmón/microbiología , Pulmón/patología , Boca/microbiología , Transducción de Señal , Microbioma Gastrointestinal/genética , Microbiota/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Polyphenolic compounds are common constituents of human and animal diets and undergo extensive metabolism by the gut microbiota before entering circulation. In order to compare the transformations of polyphenols from yerba mate, rosemary, and green tea extracts in the gastrointestinal tract, simulated gastrointestinal digestion coupled with colonic fermentation were used. For enhancing the comparative character of the investigation, colonic fermentation was performed with human, pig and rat intestinal microbiota. Chemical analysis was performed using a HPLC system coupled to a diode-array detector and mass spectrometer. Gastrointestinal digestion diminished the total amount of phenolics in the rosemary and green tea extracts by 27.5 and 59.2 %, respectively. These reductions occurred mainly at the expense of the major constituents of these extracts, namely rosmarinic acid (-45.7 %) and epigalocatechin gallate (-60.6 %). The yerba mate extract was practically not affected in terms of total phenolics, but several conversions and isomerizations occurred (e.g., 30 % of trans-3-O-caffeoylquinic acid was converted into the cis form). The polyphenolics of the yerba mate extract were also the least decomposed by the microbiota of all three species, especially in the case of the human one (-10.8 %). In contrast, the human microbiota transformed the polyphenolics of the rosemary and green extracts by 95.9 and 88.2 %, respectively. The yerba mate-extract had its contents in cis 3-O-caffeoylquinic acid diminished by 78 % by the human microbiota relative to the gastrointestinal digestion, but the content of 5-O-caffeoylquinic acid (also a chlorogenic acid), was increased by 22.2 %. The latter phenomenon did not occur with the rat and pig microbiota. The pronounced interspecies differences indicate the need for considerable caution when translating the results of experiments on the effects of polyphenolics performed in rats, or even pigs, to humans.
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Colon , Depsidos , Digestión , Fermentación , Ilex paraguariensis , Extractos Vegetales , Polifenoles , Ácido Rosmarínico , Rosmarinus , Animales , Humanos , Extractos Vegetales/metabolismo , Rosmarinus/química , Ratas , Ilex paraguariensis/química , Porcinos , Depsidos/metabolismo , Depsidos/análisis , Polifenoles/metabolismo , Polifenoles/análisis , Colon/metabolismo , Colon/microbiología , Masculino , Cinamatos/metabolismo , Cinamatos/análisis , Microbioma Gastrointestinal , Té/química , Ácido Quínico/análogos & derivados , Ácido Quínico/metabolismo , Ácido Quínico/análisis , Catequina/análogos & derivados , Catequina/metabolismo , Catequina/análisis , Cromatografía Líquida de Alta Presión , Camellia sinensis/químicaRESUMEN
Recently, hypoxic areas have been identified in water bodies of the Pampas region due to human activity. The objective of this work was to study the effect of low concentrations of dissolved oxygen (hypoxia) on the reproductive endocrine axis of a pampas fish (Odontesthes bonariensis). Groups of 8 males and 8 females were subjected to severe hypoxia (2-3 mg l-1) and normoxia (7-9 mg l-1) in 3000 l tanks by duplicate during the reproductive season (spring). After 21 days, 4 males and 4 females from each tank were sacrificed, and blood was drawn to measure estradiol (E2) and testosterone (T). The brain, pituitary gland and a portion of the gonads were extracted and processed to measure the expression of: gnrh1, cyp19a1b, fshß, lhß, fshr, lhcgr and cyp19a1a. From the second experimental week, no spawning was found in the hypoxic females, while at the end of the treatment period no male released sperm. Fish under hypoxic conditions showed signs of gonadal regression, reduction of GSI and plasma levels of sex steroids. Furthermore, the expression of gnrh1 in both sexes, cyp19a1b and fshr in males and only fshß and cyp19a1a in females decreased in comparison with normoxic fish. After 40 days under normal conditions, signs of reproductive recovery were observed in the treated fish. The results obtained demonstrated that hypoxia generated an inhibition of some components of the pejerrey's reproductive endocrine axis, but the effect was reversible.
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Introducción: La pubertad precoz se define como la aparición progresiva de signos puberales a una edad por debajo de 2,5 desviaciones estándar (DE) de la media para una población determinada. Se carece a nivel nacional de estudios epidemiológicos sobre esta afección. Objetivo: Determinar las características de la pubertad precoz para evaluar la edad de inicio de las características sexuales secundarias en una población de niñas menores de 8 años. Materiales y Métodos: El presente estudio es de tipo observacional, descriptivo, retrospectivo, de corte transversal. La población incluyó niñas menores de 8 años, que consultaron en un hospital de referencia, durante el periodo de enero de 2017 a diciembre de 2021. Como variables se analizó la edad al inicio de los síntomas, edad a la consulta, escolaridad, procedencia, motivo de consulta, signos y síntomas, cambios en edad ósea, respuesta positiva a la prueba con GnRH y asociación etiológica con cambios hallados en la RMN cerebral y ecografía pélvica; así como el abordaje terapéutico. Resultados: Ingresaron al estudio 48 pacientes de sexo femenino, menores de 8 años de edad. El inicio de los síntomas se presentó en promedio a los 5,4 +/- 2,27 años, siendo la edad de 6-7 años el 31,3% del total de pacientes. El diagnóstico predominante fue el de una pubertad precoz central y de las pruebas de estímulo con GnRH, el 68,8% resultaron positivas. Conclusión: La edad promedio de inicio del desarrollo puberal en este grupo de niñas fue 5 años, adelantado en relación a la literatura clásica, con etiología no conocida en la mayoría de los casos.
Introduction: Precocious puberty is defined as the progressive appearance of pubertal signs at an age below 2.5 standard deviations (SD) from the mean for a given population. There is a lack of epidemiological studies on this condition in our country. Objective: To determine the characteristics of precocious puberty and to evaluate the age of onset of secondary sexual characteristics in a population of girls under 8 years of age. Materials and Methods: This was an observational, descriptive, retrospective and cross-sectional study. Population: girls under 8 years of age, who consulted at a referral hospital from January 2017 to December 2021. The variables analyzed were age at the onset of symptoms, age at consultation, education, place of residence, reason for consultation, signs and symptoms, changes in bone age, positive response to the GnRH test and etiological association with changes found in brain MRI and pelvic ultrasound, as well as the therapeutic approach. Results: 48 female patients under 8 years of age entered the study. The onset of symptoms occurred on average at 5.4 +/- 2.27 years, in 31.3% of all patients at the age of 6-7 years. Predominant diagnosis was central precocious puberty and 68.8% of GnRH stimulus tests were positive. Conclusion: The average age of onset of pubertal development in this group of girls was 5 years, earlier than described in the literature, with unknown etiology in most cases.
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Phthalates, such as di-n-butyl phthalate (DBP) and di-isopentyl phthalate (DiPeP), are pollutants with a high potential for endocrine disruption. This study aimed to evaluate parameters of endocrine disruption in specimens of the Neotropical fish Rhamdia quelen exposed to DBP and DiPeP through their food. After 30 days of exposure, the fish were anesthetized and then euthanized, and blood, hypothalamus, liver, and gonads were collected. DBP caused statistically significant alterations in the serotoninergic system of males (5 and 25 ng/g) and females (5 ng/g) of R. quelen and it increased testosterone levels in females (25 ng/g). DiPeP significantly altered the dopaminergic system in females, reduced plasma estradiol levels (125 ng/g) and hepatic vitellogenin expression (25 ng/g), and changed the antioxidant system in gonads (125 ng/g). The results suggest that DBP and DiPeP may have different response patterns in females, with the former being androgenic and the latter being anti-estrogenic. These findings provide additional evidence regarding the molecular events involving DBP and DiPeP in the endocrine disruption potential in juvenile specimens of Rhamdia quelen.
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Antioxidantes , Bagres , Dibutil Ftalato , Disruptores Endocrinos , Neurotransmisores , Vitelogeninas , Animales , Vitelogeninas/metabolismo , Vitelogeninas/sangre , Dibutil Ftalato/toxicidad , Disruptores Endocrinos/toxicidad , Femenino , Antioxidantes/metabolismo , Masculino , Neurotransmisores/metabolismo , Contaminantes Químicos del Agua/toxicidad , Ácidos Ftálicos/toxicidad , Gónadas/efectos de los fármacosRESUMEN
Background: Suicide is a significant public health problem influenced by various risk factors, including dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. Zinc (Zn), essential for pituitary function in hormone synthesis and release, has been linked to suicide, with studies noting reduced serum levels and altered brain transport mechanisms. Despite Zn's crucial role in pituitary function and its involvement in suicidal behavior, information on pituitary Zn in suicide is scarce. Tumor cells modify Zn dynamics in tissues, and a previous report suggests microadenomas in the anterior pituitary as a risk factor for suicide. Methods: Histopathological analysis with hematoxylin-eosin stain and histochemical techniques to assess Zn homeostasis were carried out on anterior pituitary postmortem samples from 14 suicide completers and 9 non-suicidal cases. Results: Pituitary microadenomas were identified in 35% of suicide cases and none in the non-suicidal cases. Furthermore, compartmentalized Zn (detected via dithizone reactivity), but not free Zn levels (detected via zinquin reactivity), was lower in the suicide cases compared to the non-suicidal group. Conclusion: This is the first report of a potential association between disrupted Zn homeostasis and microadenomas in the anterior pituitary as a feature in suicide and provides critical insights for future neuroendocrine Zn-related research.
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Accumulating evidence suggests that interactions between the brain and gut microbiota significantly impact brain function and mental health. In the present study, we aimed to investigate whether young, healthy adults without psychiatric diagnoses exhibit differences in metabolic stool and microbiota profiles based on depression/anxiety scores and heart rate variability (HRV) parameters. Untargeted nuclear magnetic resonance-based metabolomics was used to identify fecal metabolic profiles. Results were subjected to multivariate analysis through principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), and the metabolites were identified through VIP score. Metabolites separating asymptomatic and symptomatic groups were acetate, valine, and glutamate, followed by sugar regions, glutamine, acetone, valerate, and acetoacetate. The main metabolites identified in high vagal tone (HVT) and low vagal tone (LVT) groups were acetate, valerate, and glutamate, followed by propionate and butyrate. In addition to the metabolites identified by the PLS-DA test, significant differences in aspartate, sarcosine, malate, and methionine were observed between the groups. Levels of acetoacetate were higher in both symptomatic and LVT groups. Valerate levels were significantly increased in the symptomatic group, while isovalerate, propionate, glutamate, and acetone levels were significantly increased in the LVT group. Furthermore, distinct abundance between groups was only confirmed for the Firmicutes phylum. Differences between participants with high and low vagal tone suggest that certain metabolites are involved in communication between the vagus nerve and the brain.
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BACKGROUND: Some evidence suggests an association between gut dysbiosis and cirrhosis progression. The authors investigated Gut Microbiome (GM) influence on 90-day mortality and hospitalization/rehospitalization rates in cirrhotic patients. METHODS: Compensated/decompensated outpatients and decompensated inpatients were prospectively included and compared to healthy controls. Clinical, laboratory, GM, and two ratios between phyla were evaluated. Patients were followed up for 90 days for hospitalization/rehospitalization and mortality. RESULTS: 165 individuals were included (50 compensated, 49 decompensated outpatients; 36 decompensated inpatients; 30 healthy), 48.5 % female, mean age was 61, main cirrhosis etiology was hepatitis C (27.3 %), and mostly Child-Pugh (CP) B patients, median MELD of 13. As liver disease progressed, microbiota diversity decreased between the groups (p = 0.05; p < 0.004). There were 9 deaths and 22 hospitalizations or rehospitalizations. GM composition had correlation with norfloxacin (p = 0.36, p = 0.04), encephalopathy (p = 0.31, p = 0.01), lactulose (p = 0.26, p = 0.01), 90-day mortality (p = 0.22, p = 0.04), CP (p = 0.17, p = 0.01), previous 6-month antibiotic use (p = 0.16, p = 0.01), MELD (p = 0.145, p = 0.01), ALBI (p = 0.1, p = 0.04) and 90-day hospitalization/rehospitalization (p = 0.08, p = 0.03). Firmicutes/Bacteroidetes (F/B) and Firmicutes/Proteobacteria (F/P) ratios were progressively lower and more significant and had an association with 90-day mortality (p < 0.001). Three MELD set-points (≥ 15, 18 and 20) were significantly associated with both ratios, with similar accuracies. CONCLUSIONS: GM dysbiosis was associated with higher CP, MELD, 90-day mortality and hospitalization/rehospitalization. F/B and F/P ratios were associated with 90-day mortality.
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Microbioma Gastrointestinal , Cirrosis Hepática , Humanos , Femenino , Masculino , Cirrosis Hepática/mortalidad , Cirrosis Hepática/microbiología , Cirrosis Hepática/complicaciones , Persona de Mediana Edad , Pronóstico , Anciano , Estudios Prospectivos , Hospitalización/estadística & datos numéricos , Estudios de Casos y Controles , Firmicutes , Disbiosis/microbiología , Disbiosis/mortalidad , Adulto , Progresión de la Enfermedad , Índice de Severidad de la Enfermedad , Heces/microbiologíaRESUMEN
Multiple Sclerosis (MS) is a debilitating disease that severely affects the central nervous system (CNS). Apart from neurological symptoms, it is also characterized by neuropsychiatric comorbidities, such as anxiety and depression. Phosphodiesterase-5 inhibitors (PDE5Is) such as Sildenafil and Tadalafil have been shown to possess antidepressant-like effects, but the mechanisms underpinning such effects are not fully characterized. To address this question, we used the EAE model of MS, behavioral tests, immunofluorescence, immunohistochemistry, western blot, and 16 S rRNA sequencing. Here, we showed that depressive-like behavior in Experimental Autoimmune Encephalomyelitis (EAE) mice is due to neuroinflammation, reduced synaptic plasticity, dysfunction in glutamatergic neurotransmission, glucocorticoid receptor (GR) resistance, increased blood-brain barrier (BBB) permeability, and immune cell infiltration to the CNS, as well as inflammation, increased intestinal permeability, and immune cell infiltration in the distal colon. Furthermore, 16 S rRNA sequencing revealed that behavioral dysfunction in EAE mice is associated with changes in the gut microbiota, such as an increased abundance of Firmicutes and Saccharibacteria and a reduction in Proteobacteria, Parabacteroides, and Desulfovibrio. Moreover, we detected an increased abundance of Erysipelotrichaceae and Desulfovibrionaceae and a reduced abundance of Lactobacillus johnsonii. Surprisingly, we showed that Tadalafil likely exerts antidepressant-like effects by targeting all aforementioned disease aspects. In conclusion, our work demonstrated that anxiety- and depressive-like behavior in EAE is associated with a plethora of neuroimmune and gut microbiota-mediated mechanisms and that Tadalafil exerts antidepressant-like effects probably by targeting these mechanisms. Harnessing the knowledge of these mechanisms of action of Tadalafil is important to pave the way for future clinical trials with depressed patients.
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Ansiolíticos , Antidepresivos , Eje Cerebro-Intestino , Depresión , Encefalomielitis Autoinmune Experimental , Inhibidores de Fosfodiesterasa 5 , Tadalafilo , Animales , Femenino , Ratones , Ansiolíticos/administración & dosificación , Antidepresivos/administración & dosificación , Autoinmunidad/efectos de los fármacos , Eje Cerebro-Intestino/efectos de los fármacos , Depresión/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Ratones Endogámicos C57BL , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Tadalafilo/administración & dosificaciónRESUMEN
OBJECTIVE: Obesity represents a significant global health challenge characterized by chronic low-grade inflammation and metabolic dysregulation. The hypothalamus, a key regulator of energy homeostasis, is particularly susceptible to obesity's deleterious effects. This study investigated the role of the immunoproteasome, a specialized proteasomal complex implicated in inflammation and cellular homeostasis, during metabolic diseases. METHODS: The levels of the immunoproteasome ß5i subunit were analyzed by immunostaining, western blotting, and proteasome activity assay in mice fed with either a high-fat diet (HFD) or a regular diet (CHOW). We also characterized the impact of autophagy inhibition on the levels of the immunoproteasome ß5i subunit and the activation of the AKT pathway. Finally, through confocal microscopy, we analyzed the contribution of ß5i subunit inhibition on mitochondrial function by flow cytometry and mitophagy assay. RESULTS: Using an HFD-fed obese mouse model, we found increased immunoproteasome levels in hypothalamic POMC neurons. Furthermore, we observed that palmitic acid (PA), a major component of saturated fats found in HFD, increased the levels of the ß5i subunit of the immunoproteasome in hypothalamic neuronal cells. Notably, the increase in immunoproteasome expression was associated with decreased autophagy, a critical cellular process in maintaining homeostasis and suppressing inflammation. Functionally, PA disrupted the insulin-glucose axis, leading to reduced AKT phosphorylation and increased intracellular glucose levels in response to insulin due to the upregulation of the immunoproteasome. Mechanistically, we identified that the protein PTEN, a key regulator of insulin signaling, was reduced in an immunoproteasome-dependent manner. To further investigate the potential therapeutic implications of these findings, we used ONX-0914, a specific immunoproteasome inhibitor. We demonstrated that this inhibitor prevents PA-induced insulin-glucose axis imbalance. Given the interplay between mitochondrial dysfunction and metabolic disturbances, we explored the impact of ONX-0914 on mitochondrial function. Notably, ONX-0914 preserved mitochondrial membrane potential and attenuated mitochondrial ROS production in the presence of PA. Moreover, we found that ONX-0914 reduced mitophagy in the presence of PA. CONCLUSIONS: Our findings strongly support the pathogenic involvement of the immunoproteasome in hypothalamic neurons in the context of HFD-induced obesity and metabolic disturbances. Targeting the immunoproteasome highlights a promising therapeutic strategy to mitigate the detrimental effects of obesity on the insulin-glucose axis and cellular homeostasis. This study provides valuable insights into the mechanisms driving obesity-related metabolic diseases and offers potential avenues for developing novel therapeutic interventions.
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Dieta Alta en Grasa , Hipotálamo , Ratones Endogámicos C57BL , Neuronas , Obesidad , Complejo de la Endopetidasa Proteasomal , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Hipotálamo/metabolismo , Obesidad/metabolismo , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Complejo de la Endopetidasa Proteasomal/metabolismo , Masculino , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/etiología , OligopéptidosRESUMEN
Stress, infections, and psychological and social well-being can affect the reproductive system. Activation of the hypothalamic-pituitary-adrenal axis can disrupt ovarian cyclicity. Estrogens can modulate stress responsiveness and mood. Thus, understanding this interaction and how it modulates the menstrual cycle is crucial for women's reproductive health. PURPOSE: The objective of this study was to analyze the influence of a stressor, a period of the Covid-19 pandemic when there were no vaccines available yet, on the psychological state of women aged 18 to 45 years; as well as the influence of mental health on the menstrual cycle, considering the influence of age and hormonal contraceptives. METHOD: Online questionnaire using the Google Forms platform was used. RESULTS: There is a high prevalence of the onset of new psychosocial symptoms. Moreover, most women reported some type of change in their menstrual cycles. The women who were using hormonal contraceptives demonstrated a higher frequency of spotting and menstrual color alterations, while women without hormonal contraceptives demonstrated a higher frequency of cycle duration and menstrual odor alterations. Women without hormonal contraceptives were more susceptible to the development of psychosocial symptoms. Younger adult women were more affected by menstrual changes and psychosocial symptoms. Close to 90% of women who reported several psychosocial symptoms had changes in their menstrual cycles. CONCLUSION: These data suggest the impact of stressors, such as a period of the pandemic, on mental health and menstrual cycles, and younger adult women can be more susceptible. This reflects the relationship between mental and reproductive health.
RESUMEN
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization in March 2020. Since then, viral spread from humans to animals has occurred worldwide. Nonhuman primates (NHPs) have been found to be susceptible to reverse-zoonosis transmission of SARS-CoV-2, but initial research suggested that platyrrhine primates are less susceptible than catarrhine primates. Here we report the natural SARS-CoV-2 infection of a common woolly monkey (Lagothrix lagothricha) from a wildlife rehabilitation center in Ecuador. The course of the disease, the eventual death of the specimen, and the pathological findings are described. Our results show the susceptibility of a new platyrrhine species to SARS-CoV-2 and provide evidence for the first time of a COVID-19-associated death in a naturally infected NHP. The putative route of transmission from humans, and implications for captive NHPs management, are also discussed. Given that common woolly monkeys are at risk of extinction in Ecuador, further understanding of the potential threat of SARS-CoV-2 to their health should be a conservation priority. A One Health approach is the best way to protect NHPs from a new virus in the same way that we would protect the human population.