Prevenção do suicídio: esquecimento do ser e era da técnica / Suicide prevention: forgetfulness of being and technical era / Prevención del suicidio: olvido del ser y la era de la técnica

Martin Heidegger, em sua ontologia, destaca uma característica específica da atualidade que atravessa o comportamento humano, na filosofia, na ciência ou no senso comum: o esquecimento do ser. O filósofo diferencia a época atual das demais épocas históricas. O horizonte histórico contemporâneo se desvela por meio do desafio e da exploração, da tentativa de controle e domínio dos acontecimentos, ao modo da disponibilidade e em função da produtividade. O filósofo esclarece que todo esse desenraizamento do homem atual está atrelado ao esquecimento daquilo que é o mais essencial, qual seja, a existência. A questão que norteia este estudo é apurar, por meio das referências de Heidegger e dos estudos sobre suicídio, o quanto a interpretação da morte voluntária nos dias atuais está atravessada por tal esquecimento. Pretendemos investigar o quanto as ações de prevenção desenvolvidas pela suicidologia se encontram atravessadas por tal esquecimento do ser do homem e, dessa forma, acabam por estabelecer relações entre ser e ente em uma consequente redução ao ente como invariante e atemporal. O caminho para investigar a questão iniciará por abordar, em maiores detalhes, a analítica existencial, a questão da técnica e o movimento de esquecimento do ser apontados por Heidegger a fim de problematizar as perspectivas científicas atuais sobre o suicídio em sua prevenção para, então, estabelecer uma compreensão fenomenológica e existencial sobre o referido fenômeno.(AU)

Martin Heidegger, in his ontology, highlights a specific characteristic of the present moment that crosses human behavior, in philosophy, science, or common sense: the forgetfulness of being. The philosopher differentiates the current age from other historical ages. The contemporary historical horizon is unveiled by the challenge and the exploration, from the attempt to control and dominate events, to the mode of standing reserve and in terms of productivity. The philosopher clarifies that all this uprooting of the current man is linked to the forgetfulness of what is the most essential, namely, the existence itself. The question that guides this study is to investigate, via Heidegger's references and studies on suicide, to what extent the interpretation of voluntary death today is crossed by such forgetfulness. We intend to investigate to what extent the prevention actions developed by suicidology are crossed by such forgetfulness of the human's being and, in this way, they end up establishing relationships between being and entity in a consequent reduction to entity as an invariant and timeless. The path to investigate the issue will start by addressing, in greater detail, the existential analytics, the question concerning technique and the movement of forgetting the being pointed out by Heidegger to problematize the current scientific perspectives on suicide and its prevention to, then, propose a phenomenological and existential understanding about the referred phenomenon.(AU)

Martin Heidegger en su ontología destaca una característica específica del presente que atraviesa el comportamiento humano, ya sea en la filosofía, la ciencia o el sentido común: el olvido del ser. El filósofo diferencia la época actual de otras épocas históricas. El horizonte histórico contemporáneo se devela el desafío y la exploración, el intento de controlar y dominar los eventos, en la modalidad de disponibilidad y en términos de productividad. Y así aclara que todo este desarraigo del hombre actual está involucrado en el olvido de lo más esencial, que es la existencia misma. A partir de las referencias a Heidegger y de los estudios sobre el suicidio, este estudio busca saber hasta qué punto la interpretación de la muerte voluntaria hoy está atravesada por este olvido. Pretendemos investigar en qué medida las acciones de prevención desarrolladas por la suicidología se encuentran atravesadas por el olvido del ser del hombre y, de esta manera, terminan por establecer relaciones entre el ser y el ente, en una consecuente reducción al ente como invariante y atemporal. Para investigar el tema se abordará inicialmente, con mayor detalle, la analítica existencial, la cuestión de la técnica y el movimiento del olvido del ser señalado por Heidegger para problematizar las perspectivas científicas actuales sobre el suicidio y su prevención y, luego, proponer una comprensión fenomenológica y existencial sobre el referido fenómeno.(AU)

Sistema de avaliação de práticas psicológicas Aluízio Lopes de Brito (SAPP) sobre políticas de cuidado / Aluízio Lopes de Brito psychological practices assessment system (SAPP) on care policies / Sistema de evaluación de prácticas psicológicas Aluízio Lopes de Brito (SAPP) sobre políticas de cuidado

O objetivo do presente manuscrito é caracterizar e descrever os fluxos do Sistema de Avaliação de Práticas Psicológicas Aluízio Lopes de Brito (SAPP), dispositivo instituído no âmbito do Sistema Conselhos de Psicologia e regulamentado pelo Conselho Federal de Psicologia através da Resolução CFP nº 15, de 18 de agosto de 2023. O SAPP surge da necessidade premente de orientação e qualificação profissionais frente às práticas emergentes que produzem o saber/ fazer da psicologia. Nesse sentido, trata-se de processo que busca orientar, qualificar e fazer conhecer práticas que sejam compatíveis ou não com o exercício profissional em psicologia. Com o trabalho realizado no SAPP serão produzidos pareceres que contribuirão minimamente para o conhecimento das fronteiras que delimitam os campos da psicologia e, por excelência, conheceremos melhor nossas próprias formas de atuação. Através da consideração do trinômio teoria-prática-ética, o CFP espera com o SAPP abrir diálogos com grupos, práticas e saberes fronteiriços e constantemente relegados pela psicologia hegemônica. Para tanto, parte do pressuposto de que os saberes e fazeres destas populações podem refinar as teorias psicológicas e fazer a psicologia avançar como ciência e profissão.(AU)

This manuscript aims to characterize and describe the flows of the Aluízio Lopes de Brito Psychological Practices Assessment System (SAPP), an instrument established within the framework of the Psychology Council System and regulated by the Federal Council of Psychology (CFP) with Resolution CFP No. 15, of August 18, 2023. The SAPP arises from the pressing need for professional guidance and qualification in the face of emerging practices that shape the knowledge/practice of psychology. In this sense, it is a process that seeks to guide, qualify, and make known practices that are compatible or not with the professional practice of psychology. The work carried out in the SAPP will produce opinions that will contribute minimally to the understanding of the boundaries that delimit the fields of psychology and, by excellence, we will better understand our own modes of operation. Considering the trinity of theory-practice-ethics, the CFP hopes with the SAPP to open dialogues with groups, practices, and knowledge that are in the borders and are constantly relegated by hegemonic psychology. To this end, it assumes that the knowledge and practices of these populations can refine psychological theories and advance psychology as a science and profession.(AU)

El objetivo de este manuscrito es caracterizar y describir los flujos del Sistema de Evaluación de Prácticas Psicológicas Aluízio Lopes de Brito (SAPP), un dispositivo establecido en el marco del Sistema de Consejos de Psicología y regulado por el Consejo Federal de Psicología a través de la Resolución CFP n.º 15, con fecha del 18 de agosto de 2023. El SAPP surge de la necesidad apremiante de orientación y calificación profesional frente a las prácticas emergentes que configuran el conocimiento y las habilidades de la psicología. En este sentido, es un proceso que busca orientar, calificar y dar a conocer prácticas que sean compatibles o no con el ejercicio profesional de la psicología. El trabajo realizado en el SAPP generará opiniones que contribuirán mínimamente a la comprensión de los límites que delimitan los campos de la psicología y, por excelencia, comprender mejor nuestras propias formas de actuación. A través de la consideración de la tríada teoría-práctica-ética, el CFP espera que con el SAPP puede llevar a cabo el diálogo con grupos, prácticas y conocimientos fronterizos y constantemente pasados por alto por la psicología hegemónica. Con este fin, se asume que los conocimientos y prácticas de estas poblaciones pueden refinar las teorías psicológicas y hacer avanzar la psicología como ciencia y profesión.(AU)

Research on Molecular Mechanism of Fructus Ligustri Lucidi against Osteoporosis based on Network Pharmacology

Abstract TCMSP platform of systematic pharmacology of traditional Chinese medicine This study aimed to investigate the molecular mechanism of Fructus Ligustri Lucidi (NZZ, Chinese abbreviation) against osteoporosis (OP) by means of network pharmacology.ChemDraw Professional 15.1 software and Molinspiration Smiles database were used to draw the chemical formulas of the components. The active ingredients and related target proteins of NZZ were searched in platform of systematic pharmacology of traditional Chinese medicine database, Drugbank, Therapeutic Target Database, SymMap and other databases. Gene Ontology(GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on the selected target through Enrichr and KEGG Automatic Annotation databases, and their mechanism was studied. A total of 29 compounds and 140 corresponding targets, including 14 key targets and 14 protein factors in protein-protein interaction core network were obtained. The key targets were tumor necrosis factor(TNF), interleukin(IL)-6R and sestrogen receptor alpha. The number of GO items was 466 (P<0.05), including 399 items of biological process (BP), 54 items of cell composition (MF) and 13 items of molecular function (CC). KEGG pathway enrichment screened 85 signaling pathways (P<0.05), including the IL-17 signaling pathway, TNF signaling pathway, advanced glycation end products and their receptors signaling pathway and cAMP signaling pathway. The active ingredients of NZZ. exert their anti-OP effects through multi-components, multi-targets and multi-pathways, which can provide new evidence for further study of their anti-OP mechanism.

Bioinformatics Analysis of Core Genes and Key Pathways in Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To screen differentially expressed gene (DEG) related to myelodysplastic syndrome (MDS) based on Gene Expression Omnibus (GEO) database, and explore the core genes and pathogenesis of MDS by analyzing the biological functions and related signaling pathways of DEG.@*METHODS@#The expression profiles of GSE4619, GSE19429, GSE58831 including MDS patients and normal controls were downloaded from GEO database. The gene expression analysis tool (GEO2R) of GEO database was used to screen DEG according to | log FC (fold change) |≥1 and P<0.01. David online database was used to annotate gene ontology function (GO). Metascape online database was used to enrich and analyze differential genes in Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction network (PPI) was constructed by using STRING database. CytoHubba and Mcode plug-ins of Cytoscape were used to analyze the key gene clusters and hub genes. R language was used to diagnose hub genes and draw the ROC curve. GSEA enrichment analysis was performed on GSE19429 according to the expression of LEF1.@*RESULTS@#A total of 74 co-DEG were identified, including 14 up-regulated genes and 60 down regulated genes. GO enrichment analysis indicated that BP of down regulated genes was mainly enriched in the transcription and regulation of RNA polymerase II promoter, negative regulation of cell proliferation, and immune response. CC of down regulated genes was mainly enriched in the nucleus, transcription factor complexes, and adhesion spots. MF was mainly enriched in protein binding, DNA binding, and β-catenin binding. KEGG pathway was enriched in primary immunodeficiency, Hippo signaling pathway, cAMP signaling pathway, transcriptional mis-regulation in cancer and hematopoietic cell lineage. BP of up-regulated genes was mainly enriched in type I interferon signaling pathway and viral response. CC was mainly enriched in cytoplasm. MF was mainly enriched in RNA binding. Ten hub genes and three important gene clusters were screened by STRING database and Cytoscape software. The functions of the three key gene clusters were closely related to immune regulation. ROC analysis showed that the hub genes had a good diagnostic significance for MDS. GSEA analysis indicated that LEF1 may affect the normal function of hematopoietic stem cells by regulating inflammatory reaction, which further revealed the pathogenesis of MDS.@*CONCLUSION@#Bioinformatics can effectively screen the core genes and key signaling pathways of MDS, which provides a new strategy for the diagnosis and treatment of MDS.

Study on anticoagulant material basis and mechanism of Trichosanthis Semen and its shell and kernel based on spectrum-effect relationship integrated molecular docking / 中国中药杂志

This study explored the anticoagulant material basis and mechanism of Trichosanthis Semen and its shell and kernel based on spectrum-effect relationship-integrated molecular docking. High performance liquid chromatography(HPLC) fingerprints of Trichosanthis Semen and its shell and kernel were established. Prothrombin time(PT) and activated partial thromboplastin time(APTT) in mice in the low-and high-dose(5, 30 g·kg~(-1), respectively) Trichosanthis Semen, the shell, and kernel groups were determined as the coagulation markers. The spectrum-effect relationship and anticoagulant material basis of Trichosanthis Semen and its shell and kernel were analyzed with mean value calculation method of Deng's correlation degree(MATLAB) and the common effective component cluster was obtained. Then the common targets of the component cluster and coagulation were retrieved from TCMSP, Swiss-TargetPrediction, GenCLiP3, GeneCards, and DAVID, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. The main anticoagulant molecular mechanism of the component cluster was verified by SYBYL-X 2.1.1. The spectrum-effect relationship of Trichosanthis Semen and its shell and kernel was in positive correlation with the dosage. The contribution of each component to anticoagulation was not the same, suggesting that the material basis for anticoagulation was different, but they have common effective components(i.e. common material basis), such as adenine(peak 3), uracil(peak 4), hypoxanthine(peak 6), xanthine(peak 9), and adenosine(peak 11). Network pharmacology showed that these components can act on multiple target proteins such as NOS3, KDR, and PTGS2, and exert anticoagulant effect through multiple pathways such as VEGF signaling pathway. They involved the biological functions such as proteolysis, cell component such as cytosol, and molecular functions. The results of molecular docking showed that the binding free energy of these components with NOS3(PDB ID: 1 D0 C), KDR(PDB ID: 5 AMN), and PTGS2(PDB ID: 4 COX) was ≤-5 kJ·mol~(-1), and the docking conformations were stable. Spectrum-effect relationship-integrated molecular docking can be used for the optimization, virtual screening, and verification of complex chemical and biological information of Chinese medicine. Trichosanthis Semen and its shell and kernel have the common material basis for anticoagulation and they exert the anticoagulant through multiple targets and pathways.

Descripción y análisis de las cadenas de contagio de COVID-19 a partir de las ontologías / Description and analysis of COVID-19 contagion chains from an ontological perspective

La COVID-19 es una enfermedad causada por el virus SARS-COV2, la cual ha provocado la muerte de miles de personas en todo el mundo. La alta transmisibilidad es uno de los factores que dificulta considerablemente su contención. El análisis de las cadenas de contagio podría ofrecer elementos de interés, tanto para los estudios virológicos como epidemiológicos. Por otra parte, las ontologías se han convertido en una tecnología ampliamente aceptada para la representación del conocimiento y su correspondiente análisis. En ese sentido, el objetivo de este trabajo fue presentar un modelo ontológico para la representación y el análisis de las cadenas de contagio por COVID-19. La ontología fue desarrollada con el lenguaje OWL (Web Ontology Language), el cual es un lenguaje formal basado en lógicas descriptivas. Por lo tanto, esta propuesta podría ayudar a inferir conocimiento sobre las cadenas de contagios y así contribuir a la lucha que lleva a efecto la comunidad científica contra la COVID-19. La adopción de esta propuesta contribuirá a agilizar el análisis de las cadenas de contagio, así como a profundizar en la búsqueda de rasgos que pudieran pasar inadvertidos utilizando otros enfoques(AU)

COVID-19 is a disease caused by the SARS-CoV-2 virus which has killed thousands of people worldwide. Its high transmissibility is a factor that considerably hinders its containment. The analysis of contagion chains could provide elements of interest for both virological and epidemiological studies. On the other hand, ontologies have become a widely accepted technology for knowledge representation and its corresponding analysis. The purpose of the study was to present an ontological model for the representation and analysis of COVID-19 contagion chains. The model was developed in OWL (Web Ontology Language), a formal language based on descriptive logics. The proposal could therefore be useful to infer knowledge about contagion chains, thus contributing to the struggle of the scientific community against COVID-19. Adoption of this proposal will help speed up the analysis of contagion chains, as well as gain insight into the search for features which could go unnoticed if other approaches are used(AU)

Exploration of the core genes in ulcerative interstitial cystitis/bladder pain syndrome

ABSTRACT Objective: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment. Materials and Methods: First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS. Results: A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained. Conclusion: The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.

Effects of high-fat diet intake during perinatal period on reflex-ontogeny and intestinal morphometry of rat offspring

Reflex-ontogeny and intestinal morphometrics were evaluated in Wistar rats whose mothers were fed on a high-fat diet during the perinatal period. Male pups (n=52) formed four experimental groups: NN (pups from mothers with lab chow diet during gestation and lactation); NH (pups from mothers with lab chow diet during pregnancy and high-fat in lactation); HH (pups from mothers with high-fat diet during gestation and lactation); HN (pups from mothers with high-fat diet during pregnancy and lab chow in lactation). The reflex ontogeny, the maturation of physical characteristics and parameters of somatic growth were evaluated during lactation. In addition, the body mass index (BMI), the specific rate of weight gain (SRWG), the Lee index, the weight of the brain and intestinal parameters were analyzed after weaning. High-fat diet during pregnancy (HH and HN groups) delayed the maturation of reflexes and physical characteristics. The high-fat diet affected somatic growth differently, reducing somatic growth parameters in the groups NH and HH and increasing in the HN group. The highest SRWG was found in group HN. SRWG and BMI were reduced in the groups NH and HH. The relative intestinal weight was reduced in the groups NH, HH and HN. The relative length of small intestine was longer in group HN than in group NN. The total height of the mucosa and size of the villous were lower in group HH than in group NN. In conclusion, high-fat diet promoted negative consequences for the development of the nervous and enteric systems of the offspring(AU)

Ontogenia refleja y morfometría intestinal fueron evaluados en crías de ratas Wistar que fueron alimentadas con una dieta alta en grasas durante el período perinatal. Los descendientes machos (n = 52) formaron cuatro grupos experimentales: NN (hijos de madres que utilizaron alimentos de laboratorio durante la gestación y la lactancia); NH (hijos de madres que comieron dieta de laboratorio durante el embarazo y dieta con un alto contenido de grasas en la lactancia); HH (hijos de madres con una dieta alta en grasas durante el embarazo y la lactancia); HN (hijos de madres que comieron una dieta alta en grasas durante el embarazo y comida de laboratorio durante la lactancia). La ontogenia refleja, la maduración de las características físicas y los parámetros de crecimiento somático durante la lactancia fueron evaluados. Además, el índice de masa corporal (IMC), la tasa específica de aumento de peso (SRWG), el índice de Lee, el peso cerebral y los parámetros intestinales fueron analizados después del destete. La dieta alta en grasas durante el embarazo (grupos HH y HN) retrasó la maduración de reflejos y características físicas. La dieta alta en grasas afectó el crecimiento somático de manera diferente, reduciendo los parámetros de crecimiento somático en los grupos NH y HH y aumentando en el grupo HN. El SRWG más grande se encontró en el grupo HN. El SRWG y el IMC se redujeron en los grupos NH y HH. El peso relativo intestinal se redujo en los grupos NH, HH y HN. La longitud relativa del intestino delgado fue mayor en el grupo HN que en el grupo NN. La altura total de la mucosa y el tamaño de las vellosidades fueron menores en el grupo HH que en el grupo NN. En conclusión, la dieta alta en grasas tuvo consecuencias negativas para el desarrollo de los sistemas nervioso y entérico de la prole(AU)

Differential expression patterns of myogenic regulatory factors in the postnatal longissimus dorsi muscle of Jeju Native Pig and Berkshire breeds along with their co-expression with Pax7

BACKGROUND: Myogenic regulatory factors (MRFs) such as MyoD, Myf6 and Myf5 play a vital role in the growth and development of muscles. Jeju Native Pig (JNP) is the top ranker in Korea amongst the indigenous livestock reared for meat purpose. Few studies covering transcript abundance of the MRFs and related to their co-expression with Pax7 in JNP have been conducted. Despite having better quality pork, JNP does not have a comparative growth rate with respect to western breeds. Therefore, the present study was designed with the objective to study the relative transcript levels of MRFs in the postnatal myogenesis of longissimus dorsi muscles in JNP and Berkshire breeds. RESULTS: Relative transcript levels were analyzed by qRT-PCR and blot expression analysis through Western blotting. Immunocytochemistry was performed to analyze their expressions at cellular levels. ToppCluster aided in the analysis of gene ontology of biological processes. The quantitative transcript levels of MyoD and Pax7 were significantly (P < 0.05) higher in Berkshire than in JNP. Myotube formation was observed under the co-expression of MyoD and Pax7. ToppCluster helped in the understanding of the linking of biological processes of the MRFs with the different signaling pathways. MyBPH had significantly (P < 0.05) high transcript levels during the chosen age groups in JNP than Berkshire. CONCLUSIONS: The current study can be helpful in understanding the genetic basis for myogenesis in postnatal stage. Moreover, it can act as stepping stone for the identification of marker genes related to body growth and meat quality in JNP.

Two new species of Knodus (Characidae: Stevardiinae) from the upper rio Tocantins basin, with evidence of ontogenetic meristic changes

Two new species from the upper rio Tocantins basin are described in Knodus based on the traditional definition of the genus. The new species are distinguished from other congeners by meristic and morphometric characters, such as the number of cusps in the premaxillary and dentary teeth, the number of scale series between dorsal-fin origin and lateral line, the orbital diameter and the body depth. With the two new species, the number of endemic species in the upper rio Tocantins basin upstream of the mouth of the rio Paranã, rises to 53 (89 to the confluence with rio Araguaia). The existence of a meristic character that changes through ontogeny (allomery), viz. the number of scale series between dorsal-fin origin and lateral line, was detected in some species of Knodus through a regression analysis. Additionally, this paper describes an unambiguous, more informative and precise new method for counting vertebrae, which will enhance the efficacy of this trait in species comparisons.(AU)

Duas novas espécies do alto rio Tocantins são descritas em Knodus com base na definição tradicional do gênero. As novas espécies são distinguidas das demais congêneres por caracteres merísticos e morfométricos, tais como o número de cúspides nos dentes do pré-maxilar e do dentário, o número de séries de escamas entre a origem da nadadeira dorsal e a linha lateral, o diâmetro da órbita e a altura do corpo. Com as duas novas espécies, o número de espécies endêmicas na bacia do alto rio Tocantins, acima da barra do rio Paranã, sobe para 53 (89 até a confluência com o rio Araguaia). A existência de um caráter merístico que muda ao longo da ontogenia (alomeria), ou seja, o número de séries de escamas entre a origem da nadadeira dorsal e a linha lateral, foi detectado em algumas espécies de Knodus com uma análise de regressão. Adicionalmente, este artigo descreve um novo método não-ambíguo, mas informativo e mais preciso, para a contagem de vértebras, que aumentará a eficácia deste caráter em comparações entre espécies.(AU)

Profiles of immune infiltration in abdominal aortic aneurysm and their associated marker genes: a gene expression-based study

Immune-mediated inflammation plays a key role in the pathology of abdominal aortic aneurysm (AAA). We aimed to use a computational approach to profile the immune infiltration patterns and related core genes in AAA samples based on the overexpression of gene signatures. The microarray datasets of AAA and normal abdominal tissues were acquired from gene expression omnibus (GEO) database. We evaluated the composition of immune infiltrates through microenvironment cell populations (MCP)-counter. Weighted gene correlation network analysis (WGCNA) was employed to construct the co-expression network and extract gene information in the most relevant module. Functional and pathway enrichment analysis was performed and immune infiltration related core genes were screened. AAA tissues had a higher level of infiltration by cytotoxic lymphocytes, NK cells, T cells, fibroblasts, myeloid dendritic cells, and neutrophils than normal aorta. The red module was strongly correlated with the infiltrating levels of T cells and cytotoxic lymphocytes. Gene ontology (GO) and pathway analyses revealed that genes in the most relevant module were mainly enriched in T cell activation, regulation of lymphocyte activation, cytokine-cytokine receptor interaction, and chemokine signaling pathway, etc. The expression of GZMK, CCL5, GZMA, CD2, and EOMES showed significant correlations with cytotoxic lymphocytes, while CD247, CD2, CD6, RASGRP1, and CD48 expression were positively associated with T cell infiltration. In conclusion, we comprehensively analyzed profiles of infiltrated immune cells in AAA tissues and their associated marker genes. Our data may provide a novel clue to indicate the underlying molecular mechanisms of AAA formation in terms of immune infiltration.

Potential targets of Euodiae Fructus in treatment of insomnia based on network pharmacology / 中国中药杂志

The acupoint application of Euodiae Fructus at Yongquan(KI1) can significantly improve the sleep quality of patients with insomnia with berberine as the main effective component for the efficacy. Nineteen active compounds and 203 drug targets were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 24 common genes of diseases and drugs were obtained. STRING 11.0 was used to construct a protein-protein interaction(PPI) network of the overlapping genes, and Matthews correlation coefficient(MCC) was employed to screen the core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results revealed that the main compounds of Euodiae Fructus, such as berberine and rutaecarpine, participated in the biological processes(such as neurotransmitter receptor activity) by regulating C-reactive protein(CRP), estrogen receptor 1(ESR1), 5-hydroxytryptamine(5-HT) receptor, and interleukin-6(IL-6) to exert sedative, anxiolytic, and antidepressant effects. Sixty 4-week-old SPF mice were randomly divided into a control group, a model group, a positive drug(diazepam tablets) group, and low-, medium-, and high-dose berberine groups. Medication with corresponding drugs was performed for one week. The results demonstrated that berberine was potent in reducing the activities and standing times of mice, down-regulating the levels of CRP and IL-6 mRNA in the hypothalamus, and up-regulating the expression of 5-HT(P<0.01); however, no significant effect on ESR1 was observed. The network of Euodiae Fructus in treating insomnia was constructed by network pharmacology and verified by tests. The findings indicated that the therapeutic efficacy of Euodiae Fructus in treating insomnia was achieved by participating in multiple biological processes, such as neurotransmitter receptor activity, which provided a scientific basis for its clinical application.

Study on mechanism of Bushen Culuan Formula in treatment of polycystic ovary syndrome based on network pharmacology and molecular docking / 中国中药杂志

This study used network pharmacology and molecular docking to study the mechanism of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS). The active ingredients and potential drug targets of Bushen Cu-luan Decoction were obtained by searching the Traditional Chinese Medicine System Pharmacology(TCMSP) database, and the targets of PCOS by searching GeneCards. After the drug targets and disease targets were corrected by Uniprot, the intersection genes were obtained. STRING database and Cytoscape 3.7.2 were used for protein-protein interaction(PPI) analysis of the intersection genes. The ClueGO plug-in of Cytoscape 3.7.2 was employed to perform gene ontology(GO) enrichment and KEGG pathway enrichment for the intersection genes. Finally, molecular docking of the key active ingredients with the targets of Bushen Culuan Formula was performed using AutoDockVina and MGLtools. A total of 136 active ingredients and 314 drug targets of the decoction were obtained from TCMSP, and 136 disease targets from GeneCards. Finally, 49 drug-disease intersection genes were obtained. GO enrichment found that the genes were mainly involved in the regulation of muscle cell apoptosis, positive regulation of small molecule metabolism, core promoter binding, RNA polymerase Ⅱ regulation of pri-miRNA transcription, negative regulation of transmembrane transport and other biological functions. The enriched KEGG pathways mainly included MAPK, PI3 K-Akt, p53, and HIF-1 signaling pathways. The results of molecular docking showed that quercetin and PTGS2 can bind stably and interact through amino acid residues THR206, TRP387, ASN382, etc. This study preliminarily reveals the multi-component, multi-target, and multi-pathway mechanism of Bushen Culuan Formula in the treatment of PCOS-related infertility, which provides a basis for further research.

Met-Controlled Allosteric Module of Neural Generation as A New Therapeutic Target in Rodent Brain Ischemia / 中国结合医学杂志

OBJECTIVE@#To investigate a Met-controlled allosteric module (AM) of neural generation as a potential therapeutic target for brain ischemia.@*METHODS@#We selected Markov clustering algorithm (MCL) to mine functional modules in the related target networks. According to the topological similarity, one functional module was predicted in the modules of baicalin (BA), jasminoidin (JA), cholic acid (CA), compared with I/R model modules. This functional module included three genes: Inppl1, Met and Dapk3 (IMD). By gene ontology enrichment analysis, biological process related to this functional module was obtained. This functional module participated in generation of neurons. Western blotting was applied to present the compound-dependent regulation of IMD. Co-immunoprecipitation was used to reveal the relationship among the three members. We used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion group. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were supposed to show the changing circumstances for neural generation under cerebral ischemia.@*RESULTS@#Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group (P<0.05). Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory activities. An anti-ischemic excitatory allosteric module (AM@*CONCLUSIONS@#AM

Scr eening of key genes and pathways of brain aging and prediction of potential effective Chinese medicinals: based on bioinformatics / 中国中药杂志

Microarray data of hippocampal tissue(HC) of the cognitively intact elderly(60-99 years old) were compared with those of the middle-aged and the young(20-59 years old) by bioinformatics techniques to initially screen out differentially expressed genes(DEGs) and then predict potential effective Chinese medicinals for the treatment of brain aging. The gene expression profile(accession: GSE11882) was downloaded from the Gene Expression Omnibus(GEO) and DEGs were screened based on R package. The key DEGs were identified by STRING, Cytoscape and the plug-in, followed by Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Then the key genes and the medical ontology information retrieval platform(Coremine Medical) were mapped against each other to single out the Chinese medicinals for the treatment of brain aging and construct the " Chinese medicinal-active constituent-target" network. Among the resultant 268 DEGs(246 down-regulated and 22 up-regulated), the 15 key genes were mainly involved in biological processes such as leukocyte migration, neutrophil activation, cell chemotaxis, microglia activation and response to external stimulus, and pathways such as inflammatory process, immune response, cytokine-cytokine receptor interaction, PI3 K-Akt signaling pathway, Rap1 signaling pathway, chemokine signaling pathway and Toll-like receptor signaling pathway. The potential effective Chinese medicinals were Notoginseng Radix et Rhizoma, Ginseng Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma and Astragali Radix. The analysis of DEGs and key genes enhances the understanding of the mechanisms of brain aging. This study provides potential gene targets and ideas for the development of Chinese medicine for brain aging.

Mechanism and experimental verification of Dachengqi Decoction in treatment of sepsis based on network pharmacology / 中国中药杂志

This study aims to predict the material basis and mechanism of Dachengqi Decoction in the treatment of sepsis based on network pharmacology. The chemical constituents and targets of Dachengqi Decoction were retrieved from TCMSP, UniPot and DrugBank and the targets for the treatment of sepsis from OMIM and GeneCards. The potential targets of Dachengqi Decoction for the treatment of sepsis were screened by OmicShare. STRING database and Cytoscape 3.7.2 were used to construct the Chinese medicinal-active component-target-disease, active component-key target-key pathway, and protein-protein interaction(PPT) networks. The gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID(P<0.05). Finally, the animal experiment was conducted to verify some targets and pathways. A total of 40 active components and 157 targets of the Dachengqi Decoction, 2 407 targets for the treatment of sepsis, and 91 common targets of the prescription and the disease were also obtained. The key targets were prostaglandin G/H synthase 2(PTGS2), prostaglandin G/H synthase 1(PTGS1), protein kinase cAMP-dependent catalytic-α(PRKACA), coagulation factor 2 receptor(F2 R), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic gamma subunit(PIK3 CG), dipeptidyl peptidase 4(DPP4), etc. A total of 533 terms and 125 pathways were obtained for the 91 targets. The main terms were the response to drug, negative regulation of apoptotic process, positive regulation of nitric oxide biosynthetic process and lipopolysaccharide-mediated signaling pathway, and the pathways included pathways in cancer, hepatitis B, and phosphatidylinositol 3-kinase and protein kinase B(PI3 K/Akt) signaling pathway. The animal experiment confirmed that Dachengqi Decoction can down-regulate inflammatory cytokines interleukin-1β(IL-1β), IL-6 and tumor necrosis factor α(TNF-α)(P<0.01). It could also reduce the wet/dry weight ratio of lung tissue, the level of myeloperoxidase(MPO) and the phosphorylation of PI3 K and Akt(P<0.01). These results indicated that Dchengqi Decoction could act on inflammation-related targets and improve sepsis by inhibiting PI3 K/Akt signaling pathway. The animal experiment supported the predictions of network pharmacology. Dachengqi Decoction intervenes sepsis via multiple components, multiple targets, and multiple pathways. The result lays a foundation for further research on the mechanism of Dachengqi Decoction in the treatment of sepsis.

Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration / 中华医学杂志(英文版)

BACKGROUND@#Age-related macular degeneration (AMD) is the leading cause of vision loss worldwide. However, the mechanisms involved in the development and progression of AMD are poorly delineated. We aimed to explore the critical genes involved in the progression of AMD.@*METHODS@#The differentially expressed genes (DEGs) in AMD retinal pigment epithelial (RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564, which were downloaded from the gene expression omnibus database. The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The hub genes were identified from these DEGs through protein-protein interaction network analyses. The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866. Following the identification of AMD-related key genes, the potential small molecule compounds targeting the key genes were predicted by PharmacoDB. Finally, a microRNA-gene interaction network was constructed.@*RESULTS@#Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples. These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication, cell cycle, and proteasome-mediated protein polyubiquitination. Among the top ten hub genes, HSP90AA1, CHEK1, PSMA4, PSMD4, and PSMD8 were upregulated in the senescent ARPE-19 cells. Additionally, the drugs targeting HSP90AA1, CHEK1, and PSMA4 were identified. We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE.@*CONCLUSIONS@#Based on our findings, HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD. Targeting HSP90AA1, CHEK1, PSMA4, PSMD4, and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence.

Complexity, Basis of the Epistemological and Ontological Approach for the Development of General Job Competences / La complejidad: base del enfoque epistemológico y ontológico para el desarrollo de competencias laborales generales

RESUMEN Las competencias laborales generales (CLG) como aspectos asociados a la productividad y la competitividad buscan la formación de personas que emprendan proyectos de vida que les posibilite desempeñarse con éxito en su quehacer laboral, por ello estas competencias preparan a los jóvenes en la responsabilidad de ser productivos para sí mismos y para los demás, en atención a los retos sociales, económicos, culturales y tecnológicos. Lo anterior exige el reconocimiento de bases epistémicas y ontológicas para la generación y el desarrollo de esa competencia. Este artículo realiza un acercamiento a estas bases y explica las relaciones ante el nuevo paradigma de la complejidad, brinda cuatro postulados en los que se explica por qué la formación en CLG exige una mirada no mecanicista, ni reduccionista, ni fragmentada, que permita comprender la formación y dar nuevas pistas ante las reducidas miradas de educación en los territorios.

ABSTRACT The General Job Competencies (GJC), as aspects associated with productivity and competitiveness, seek to train people to undertake life projects that enable them to perform successfully in their work tasks. For this reason, these competencies prepare young people in the responsibility of being productive for themselves and for others; taking into account social, economic, cultural, and technological challenges. This requires the recognition of epistemic and ontological bases for the generation and development of these competencies. This article makes an approach to these bases, explaining the relationships in the face of the new paradigm of complexity, and provides four postulates where it is explained why training at GJC requires a non-mechanistic, reductionist, or fragmented view that allows for an understanding of the training, and for giving new clues to the reduced views of education in the territories.

Network prediction of the potential molecular mechanisms in birds of prey exposed to organochlorine pesticides / Red de predicción de potenciales mecanismos moleculares en aves de presa expuestas a pesticidas organoclorados

Abstract In the 1960s, organochlorine compounds were responsible for the decline of birds of prey populations such as Haliaee- tus leucocephalus and Falco peregrinus. Pesticides similar to DDT cause bioaccumulation in birds, affecting their eggshell com- position and compromising their development. Using system biology tools, the goal of this study was to better comprehend how organochlorines act on birds. We performed a literature review, using the STITCH 5.0 platform, searching for the terms DDT and TCDD. The sub-networks were amplified in 100 interactions in STRING 10.5 and joined by the Cytoscape 3.4.0 Merge software, using the experimental animal model Gallus gallus. Clusterization, gene ontology, and centrality were the parameters evaluated in the resulting network. The resulting network had 1,417 interactions and 137 nodes. The clusterization indicated four clusters and the gene ontology pointed to biological processes related to cell signaling and morphological development. The centrality analysis indicated ESR1 and HSP90AB1 as hub/bottleneck proteins involved in the estrogen pathway and calcium transport. Therefore, it is possible that HSP90 proteins have increased expression in birds contaminated with organochlorine pesticides, favoring ESRI-organochlorines interaction and disturbing the calcium availability related to the eggshell formation. The presence or absence of heat shock proteins, such as HSP90, influences several aspects of reproduction in many species. Therefore, the relationship between the HSP90 protein expression and thin-shell syndrome was identified for the first time in this in silico study.

Resumen En los años 60, los organoclorados fueron responsables del declive de aves de rapiña como Haliaeetus leucocephalus y Falco peregrinus. Pesticidas como el DDT, causan biomagnificación en las aves, afectando las cáscaras de los huevos y dañando su desarrollo. El objetivo de este trabajo fue, a través de herramientas de biología de sistemas, comprender cómo los organoclorados actúan en el organismo de las aves. A través de una revisión bibliográfica se incluyeron dos compuestos, DDT y TCDD. Estos fue ron prospectos en la plataforma STITCH 5.0. Las subredes encontradas fueron aumentadas en 100 interacciones en la plataforma STRING 10.5 y unidas por la herramienta Merge del programa Cytoscape 3.4.0, usando el modelo experimental Gallus gallus. En la red resultante se analizaron la clusterización, la ontología génica y la centralidad. La red resultante presentó 137 nudos y 1.417 interacciones. El análisis de clusterización indicó 4 clusters, siendo que el análisis y ontología génica apuntó procesos biológicos ligados a la señalización y al desarrollo morfológico. El estudio de centralidad apuntó a ESR1 y HSP90AB1 como los hubs-bottle- neck proteínas que estaban involucradas en la vía de recepción de estrógeno y en el transporte de calcio. De acuerdo con los resultados podemos inferir que las proteínas HSP90 tienen su expresión aumentada, en aves contaminadas con pesticidas organoclo rados, favoreciendo la interacción entre ESRI y DDT / TCDD. Con ello, la interacción ESRI y la hormona estrógeno se compromete perjudicando el transporte de calcio y consecuentemente la formación de la cáscara del huevo en aves expuestas. La expresión de proteínas de choque térmico ha sido asociada a varios aspectos de la reproducción en muchas especies, sin embargo, una asociación entre HSP90 y el síndrome de la cáscara fina del huevo fue identificada por primera vez en este experimento in silico.