Phylogenetic relationships of the Mangrove Hummingbird, "Amazilia" boucardi (Apodiformes: Trochilidae) of Costa Rica / Relaciones filogenéticas del Colibrí manglero "Amazilia" boucardi (Apodiformes: Trochilidae) de Costa Rica

Abstract Introduction: A recent revision of the generic classification of the Trochilidae based on DNA sequences revealed many inconsistencies with the current generic classification, largely based on plumage characters subject to homoplasy, especially in the Trochilini, the largest tribe. A thorough generic reorganization brought the classification into accord with the phylogeny, but due to lack of genetic data, two species remained unclassified. One of these was the Mangrove Hummingbird, "Amazilia" boucardi, endemic to Costa Rica and included in the IUCN red list of threatened species. Objective: To obtain molecular evidence to clarify the generic relationships of "A." boucardi. Methods: We isolated DNA from tissues of this species and amplified 4 nuclear and 4 mitochondrial fragments and compared these with homologous fragments from 56 species in the Trochilini, constructing phylogenetic trees with maximum likelihood and Bayesian methods. Results: Our phylogenetic analyses confirmed the placement of boucardi in the Trochilini and definitely excluded it from Amazilia but placed it with high confidence in the genus Chrysuronia Bonaparte, 1850, within which its closest relative is C. coeruleogularis, which also inhabits mangroves. Conclusions: Our genetic data based on nuclear and mitochondrial regions clearly indicate the relationship of A. boucardi and L. coeruleogularis. Moreover, it is also supported by their habitat distribution in the mangroves of the Pacific coast of Costa Rica and Western Panama. Therefore, we suggested to exclude A. boucardi as "incertae sedis".

Resumen Introducción: Una revisión reciente de la clasificación de la familia Trochilidae con base en secuencias de ADN demostró muchas incongruencias con la clasificación genérica previa, que había sido hecho con base en caracteres del plumaje muy sujetos a homoplasia, especialmente en la tribu más grande, Trochillini. Una reorganización de los géneros logró llevar su clasificación genérica a la concordancia con la filogenia, pero debido a la ausencia de datos genéticos, dos especies permanecieron sin clasificar. Una de estas fue el colibrí de manglar Amazilia boucardi, una especie endémica de Costa Rica, considerada como amenazada en la lista roja de la UICN. Objetivo: Obtener evidencia molecular para esclarecer las relaciones genéricas de A. boucardi. Métodos: Se aisló ADN de tejidos de esta especie y se amplificaron 4 fragmentos de ADN del núcleo y 5 de la mitocondria, y se compararon con fragmentos homólogos de 56 especies en la tribu Trochillini, generando árboles filogenéticos con métodos de máxima verosimilitud y bayesiano. Resultados: Los análisis filogénticos obtenidos confirmaron la ubicación de boucardi en Trochilini y definitivamente la excluyó del género Amazilia, pero la ubicó con un alto grado de confianza en el género Chrysuronia Bonaparte, 1850, dentro los cuales su pariente más cercano es C. coeruleogularis, que también habita manglares. Conclusiones: Nuestros datos genéticos basados en regiones nucleares y mitocondriales indican claramente la relación entre A. boucardi and L. coeruleogularis. Es más, lo anterior se sustenta por su distribución en los manglares de la costa Pacífica de Costa Rica y oeste de Panamá. Por lo tanto, sugerimos excluir a A. boucardi como "incertae sedis".

Homologous recombination deficiency gene panel analysis results in synchronous endometrial and ovarian cancers

SUMMARY OBJECTIVE: The objective of this study was to analyze the genetic alterations of tumors within the scope of the homologous recombination deficiency gene panel in patients diagnosed with synchronous endometrial ovarian cancer who have been followed for over 5 years using next-generation sequencing. METHODS: DNA was isolated from the patient's formalin-fixed, paraffin-embedded tissue blocks. Next-generation sequencing was performed using the Illumina capture-based sequencing method. Samples were sequenced using the Sophia HR Solution DNA Kit. RESULTS: Seven patients were included in this study. The ratios of likely pathogenic (LP)/pathogenic (P) somatic mutations in ATM (serine/threonine kinase or Ataxia-telangiectasia mutated gene), BRCA2 (breast cancer type 2 susceptibility gene), BARD1 (BRCA1 associated RING domain 1), TP53 (tumor protein p53), BIRP1 (BRCA1-interacting helicase 1 gene), PALB2 (partner and localizer of BRCA2), and CHECK2 were 21 (48.8%), 8 (18.6%), 5 (11.6%), 3 (6.9%), 2 (4.6%), 2 (4.6%), and 2 (4.6%), respectively, in endometrium, and the ratios of somatic mutations in ATM, BRCA2, TP53, BARD1, RAD54L (DNA repair/recombination protein like), BIRP1, and RAD51D (RAD51 recombinase paralog D) were 24 (60%), 6 (15%), 5 (12.5%), 2 (5%), 2 (5%), 1 (2.5%), and 1 (2.5%), respectively, in ovary. In endometrioid-synchronous endometrial ovarian cancer cases, P/LP mutations were observed in ATM and CHECK2 genes in endometrium and ATM, BRCA2, and TP53 genes in ovary. In two non-endometrioid-synchronous endometrial ovarian cancer cases, CHEK2 (checkpoint kinase 2) mutations were observed in endometrium and ATM and TP53 mutations in ovary, whereas in one case, P/LP mutations in ATM and TP53 genes were common in both tissues. CONCLUSION: Pathogenic variations confirming the diagnosis of synchronous endometrial ovarian cancer with genetic alterations were identified in all but one case. ATM gene mutation emerged as the most common alteration and has a potential association with a favorable prognosis.

Características de la Diabetes del adulto de inicio juvenil y su diagnóstico en el laboratorio / Characteristics of Maturity Onset Diabetes of the Young and its diagnosis in the laboratory / Características do diabetes adulto de início juvenil e seu diagnóstico laboratorial

La Diabetes del adulto de inicio juvenil, es un subtipo hereditario poco común que se manifiesta a una edad temprana, relacionado con mutaciones en genes específicos que principalmente afectan la función de las células beta pancreática. Un diagnóstico preciso es fundamental para un tratamiento efectivo, aunque puede ser desafiante debido a la variabilidad en sus características clínicas y moleculares. Esta revisión analiza la evidencia disponible sobre estas características y los métodos de diagnóstico utilizados en laboratorio. Se realizó una búsqueda exhaustiva en bases de datos científicas, seleccionando estudios relevantes según criterios específicos. Se analizaron características clínicas, hallazgos moleculares y métodos de diagnóstico, utilizando tablas, gráficos y síntesis narrativas. Se identificaron mutaciones genéticas asociadas con MODY, así como biomarcadores útiles en el laboratorio clínico. Además, se describieron métodos de diagnóstico molecular, incluyendo la secuenciación de próxima generación (NGS). Esta revisión resalta la importancia del diagnóstico preciso de MODY, subrayando la diversidad de sus características biológicas y moleculares, y la necesidad de una investigación más profunda para mejorar su identificación y manejo clínico

Maturity Onset Diabetes of the Young is a rare hereditary subtype that manifests at an early age, related to mutations in specific genes that primarily affect the function of pancreatic beta cells. An accurate diagnosis is crucial for effective treatment, though it can be challenging due to variability in clinical and molecular characteristics. This review examines available evidence on these characteristics and laboratory diagnostic methods. A comprehensive search was conducted in scientific databases, selecting relevant studies based on specific criteria. Clinical features, molecular findings, and diagnostic methods were analyzed using tables, graphs, and narrative synthesis. Genetic mutations associated with MODY were identified, as well as useful biomarkers in clinical laboratory settings. Additionally, molecular diagnostic methods were described, including next-generation sequencing (NGS). This review emphasizes the importance of precise MODY diagnosis, highlighting the diversity of its biological and molecular characteristics, and the need for further research to enhance its identification and clinical management

A diabetes adulto de início juvenil é um subtipo hereditário raro que se manifesta em uma idade precoce, relacionado a mutações em genes específicos que afetam principalmente a função das células beta do pâncreas. Um diagnóstico preciso é fundamental para um tratamento eficaz, embora possa ser desafiador devido à variabilidade em suas características clínicas e moleculares. Esta revisão analisa a evidência disponível sobre essas características e os métodos de diagnóstico utilizados em laboratório. Foi realizada uma busca abrangente em bases de dados científicas, selecionando estudos relevantes com base em critérios específicos. Características clínicas, descobertas moleculares e métodos de diagnóstico foram analisados utilizando tabelas, gráficos e síntese narrativa. Foram identificadas mutações genéticas associadas ao MODY, assim como biomarcadores úteis em laboratório clínico. Além disso, foram descritos métodos de diagnóstico molecular, incluindo a sequenciação de próxima geração (NGS). Esta revisão enfatiza a importância do diagnóstico preciso do MODY, destacando a diversidade de suas características biológicas e moleculares e a necessidade de uma pesquisa mais aprofundada para melhorar sua identificação e manejo clínico

Características de la Diabetes del adulto de inicio juvenil y su diagnóstico en el laboratorio

La Diabetes del adulto de inicio juvenil, es un subtipo hereditario poco común que se manifiesta a una edad temprana, relacionado con mutaciones en genes específicos que principalmente afectan la función de las células beta pancreática. Un diagnóstico preciso es fundamental para un tratamiento efectivo, aunque puede ser desafiante debido a la variabilidad en sus características clínicas y moleculares. Esta revisión analiza la evidencia disponible sobre estas características y los métodos de diagnóstico utilizados en laboratorio. Se realizó una búsqueda exhaustiva en bases de datos científicas, seleccionando estudios relevantes según criterios específicos. Se analizaron características clínicas, hallazgos moleculares y métodos de diagnóstico, utilizando tablas, gráficos y síntesis narrativas. Se identificaron mutaciones genéticas asociadas con MODY, así como biomarcadores útiles en el laboratorio clínico. Además, se describieron métodos de diagnóstico molecular, incluyendo la secuenciación de próxima generación (NGS). Esta revisión resalta la importancia del diagnóstico preciso de MODY, subrayando la diversidad de sus características biológicas y moleculares, y la necesidad de una investigación más profunda para mejorar su identificación y manejo clínico.

Maturity Onset Diabetes of the Young is a rare hereditary subtype that manifests at an early age, related to mutations in specific genes that primarily affect the function of pancreatic beta cells. An accurate diagnosis is crucial for effective treatment, though it can be challenging due to variability in clinical and molecular characteristics. This review examines available evidence on these characteristics and laboratory diagnostic methods. A comprehensive search was conducted in scientific databases, selecting relevant studies based on specific criteria. Clinical features, molecular findings, and diagnostic methods were analyzed using tables, graphs, and narrative synthesis. Genetic mutations associated with MODY were identified, as well as useful biomarkers in clinical laboratory settings. Additionally, molecular diagnostic methods were described, including next-generation sequencing (NGS). This review emphasizes the importance of precise MODY diagnosis, highlighting the diversity of its biological and molecular characteristics, and the need for further research to enhance its identification and clinical management.

A diabetes adulto de início juvenil é um subtipo hereditário raro que se manifesta em uma idade precoce, relacionado a mutações em genes específicos que afetam principalmente a função das células beta do pâncreas. Um diagnóstico preciso é fundamental para um tratamento eficaz, embora possa ser desafiador devido à variabilidade em suas características clínicas e moleculares. Esta revisão analisa a evidência disponível sobre essas características e os métodos de diagnóstico utilizados em laboratório. Foi realizada uma busca abrangente em bases de dados científicas, selecionando estudos relevantes com base em critérios específicos. Características clínicas, descobertas moleculares e métodos de diagnóstico foram analisados utilizando tabelas, gráficos e síntese narrativa. Foram identificadas mutações genéticas associadas ao MODY, assim como biomarcadores úteis em laboratório clínico. Além disso, foram descritos métodos de diagnóstico molecular, incluindo a sequenciação de próxima geração (NGS). Esta revisão enfatiza a importância do diagnóstico preciso do MODY, destacando a diversidade de suas características biológicas e moleculares e a necessidade de uma pesquisa mais aprofundada para melhorar sua identificação e manejo clínico.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study

Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Análisis bibliométrico de la investigación en genética y la ruptura de ligamento cruzado anterior en deporte: una revisión / Bibliometric analysis of research in genetic and anterior cruciate ligament rupture in sport: a review / Análise bibliométrica da pesquisa em genética e ruptura do ligamento cruzado anterior no esporte: uma revisão

Resumen: Introducción: El componente genético se ha establecido como un factor de riesgo considerable para la ruptura del ligamento cruzado anterior (RLCA). La investigación actual se ha centrado en conocer los genes candidatos que pueden influir y predisponer a un sujeto a padecer esta lesión. Objetivo: Se llevó a cabo un análisis bibliométrico para rastrear los resultados de la indagación e identificar las tendencias globales, así como las brechas en el conocimiento sobre la relación entre el componente genético y la RLCA. Metodología: Los datos fueron extraídos de las bases Pubmed y Scopus, igual que analizados en el paquete Bibliometrix del software R. Se identificó un total de 63 estudios publicados a partir del 2007. Resultados: La mayoría de las publicaciones identificadas fueron artículos de investigación (85.71 %). Los autores con mayor número de aquellas se encuentran en Polonia y Sudáfrica. El análisis a través del mapa de coocurrencias reveló que hay una línea principal de investigación basada en el estudio de polimorfismos genéticos, especialmente en los genes de las familias del colágeno (COL1A1, COL5A1, COL12A1, en mayor frecuencia). Un total de 54 genes candidatos fueron identificados en los estudios. Conclusión: Esperamos que este estudio pueda contribuir a encontrar puntos claves y vacíos de investigación, al proporcionar análisis integrales e información estructurada sobre este tema.

Abstract: Introduction: Genetic component has been established as a significant risk factor for anterior cruciate ligament rupture (ACLR). Current research has focused on knowing the candidate genes that can influence and predispose a subject to this injury. Objective: A bibliometric analysis was carried out to trace the results of the research and identify global trends and gaps in knowledge about the relationship between the genetic component and ACLR. Methodology: Data were extracted from the Pubmed and Scopus databases and analyzed in the Bibliometrix package of the R software. A total of 63 studies published since 2007 were identified. Results: Most of the publications recovered were research articles (85.71%). The authors with the highest number of those are in Poland and South Africa. The analysis through the co-occurrence map reveals that there is a mainline of research based on the study of genetic polymorphisms, especially in the genes of the collagen families (COL1A1, COL5A1, COL12A1, in greater frequency). A total of 54 candidate genes were identified within the studies. Conclusion: We hope that this study can help to find key points and research gaps by providing a comprehensive analysis and structured information on this topic.

Resumo: Introdução: O componente genético foi estabelecido como um fator de risco significativo para a ruptura do ligamento cruzado anterior (RLCA). As pesquisas atuais têm se concentrado em identificar os genes candidatos que podem influenciar e predispor um indivíduo a essa lesão. Objetivo: Foi realizada uma análise bibliométrica para rastrear os resultados das pesquisas e identificar tendências globais e lacunas no conhecimento sobre a relação entre o componente genético e a RLCA. Metodologia: Os dados foram extraídos das bases de dados Pubmed e Scopus e analisados no pacote Bibliometrix do software R. Um total de 63 estudos publicados desde 2007 foram identificados. Resultados: A maioria das publicações recuperadas foram artigos de pesquisa (85,71%). Os autores com o maior número dessas publicações estão na Polônia e na África do Sul. A análise por meio do mapa de coocorrência revela que há uma linha principal de pesquisa baseada no estudo de polimorfismos genéticos, especialmente nos genes das famílias de colágeno (COL1A1, COL5A1, COL12A1, com maior frequência). Um total de 54 genes candidatos foram identificados nos estudos. Conclusão: Esperamos que este estudo possa ajudar a encontrar pontos-chave e lacunas de pesquisa, fornecendo uma análise abrangente e informações estruturadas sobre este tema.

Perfil molecular de cáncer de endometrio en mujeres de Bogotá DC, Colombia / Molecular profile of endometrial cancer in women from Bogota DC, Colombia

Introducción: El cáncer de endometrio ocupa el sexto lugar en incidencia del cáncer en mujeres. La caracterización molecular de este cáncer permite optimizar la estratificación de riesgo para mejorar el tratamiento de las pacientes. Objetivo: Determinar el perfil molecular TCGA de pacientes con cáncer de endometrio en Bogotá, D.C., Colombia. Método: Estudio descriptivo en una cohorte de pacientes con cáncer de endometrio. Las mutaciones en los exones 9 a 14 del gen POLE fueron identificadas mediante amplificación por reacción en cadena de la polimerasa, seguida de secuenciación Sanger y análisis bioinformático. La expresión de las proteínas MMR y p53 se identificó mediante inmunohistoquímica. Resultados: Se incluyeron 40 pacientes con una mediana de edad de 66 años. El 15% presentaron mutaciones en el dominio exonucleasa de POLE. El 32% de las pacientes que no presentaron mutaciones manifestaron deficiencia en el sistema MMR. El 43,47% de las pacientes sin mutaciones en POLE ni alteración del sistema MMR presentaron alteración de la proteína p53. Conclusiones: La población de cáncer de endometrio analizada presenta un perfil molecular TCGA similar a lo reportado para otras poblaciones.

Introduction: Endometrial cancer ranks sixth in cancer incidence among women. Its molecular characterization allows for a more precise risk stratification with the aim of improving patient treatment. Objective: To determine the TCGA molecular profile of patients with endometrial cancer in Bogota, Colombia. Method: A descriptive study of a cohort of patients with endometrial cancer. The expression of MMR proteins and p53 was identified through immunohistochemistry. Mutations in exons 9 to 14 of the POLE gene were identified through polymerase chain reaction amplification, followed by Sanger sequencing and bioinformatic analysis. Results: Forty patients were included in the study, with a median age of 66 years, 15% of them exhibited mutations in the exonuclease domain of POLE, while 32% of patients without mutations showed deficiency in the MMR system. Forty three percent of patients without mutations in POLE or MMR alterations showed aberrant p53 protein expression. Conclusions: The analyzed population of endometrial cancer presents a TCGA molecular profile similar to that reported for other populations.

Mining of Gene Modules and Identification of Key Genes for Early Diagnosis of Gastric Cancer

Gastric cancer (GC) is one of the most common malignant tumors with high incidence and mortality rates. Most patients with GC are not diagnosed until the advanced stage of cancer or during tumor screening, resulting in missing the best treatment time. This study identified key modules and hub genes associated with GC by weighted gene co-expression network analysis (WGCNA). The "limma" package in R was used to identify differentially expressed genes (DEGs) in GC samples from TCGA, and a total of 4892 DEGs were identified. GO enrichment and KEGG pathway enrichment analyses were conducted to detect the related pathways and functions of DEGs. These DEGs were primarily associated with extracellular matrix organization, DNA replication, cell cycle, and p53 signaling pathway. Gene modules associated with clinical characteristics were identified with WGCNA in tumor and normal samples. Six gene modules were obtained in the WGCNA network, of which two modules were significantly correlated with GC. Hub genes of key modules were identified using survival analysis and expression analysis. Finally, one-way ANOVA was used to explore the relationship between hub gene expression in normal tissues and different pathological stages of GC. Through survival and expression analysis, a total of 19 genes with good prognosis and significantly differential expressed were identified. The hub genes were significantly differential expressed in normal tissues and different pathological stages of GC, indicating that these genes have important diagnostic value for early GC and can be used as auxiliary indicators in the diagnosis of early GC.

Detección de hemoglobinopatías en gestantes cubanas del programa: Anemias por Hematíes Falciformes en Cuba

Fundamento: La detección prenatal de hemoglobinopatías en Cuba se realiza a todas las gestantes en la atención Primaria de Salud, a través de la electroforesis de hemoglobina para identificar parejas de alto riesgo. El programa brinda asesoramiento genético, diagnóstico prenatal molecular e interrupciones selectivas de fetos afectados, a solicitud de las parejas. Objetivo: Determinar el tipo y frecuencia de hemoglobinopatías en gestantes cubanas. Método: Se realizó un estudio descriptivo, retrospectivo y de corte transversal para determinar el tipo de hemoglobinopatías en 1 342 917 gestantes captadas en un periodo de diez años. El método de pesquisa fue la electroforesis de hemoglobina en geles de agarosa a pH alcalino. La confirmación por electroforesis de hemoglobina en gel de agarosa a pH ácido, ambos métodos mediante el equipo Hydrasys 2. Resultados: La frecuencia global de gestantes con hemoglobinopatías fue de 3,5 %. Se detectó hemoglobinopatías en 47 465 mujeres; 38 698 con variante S heterocigoto, 8 706 variantes de hemoglobina C y 158 de otras variantes. Se detectaron 44 283 esposos con hemoglobinopatías, 3 099 parejas de alto riesgo y se realizaron 2 689 diagnósticos prenatales moleculares. Se confirmaron 522 fetos afectados y 382 parejas solicitaron la interrupción del embarazo. El programa alcanzó 99,24 % de cobertura en el país. Conclusiones: La detección de las hemoglobinopatías en gestantes residentes en Cuba, permitió conocer el tipo de hemoglobinopatía y la frecuencia de hemoglobinas anormales y nuevas variantes, de ahí el interés de continuar el programa de pesquisa para prevenir la aparición de formas graves de la enfermedad.

Foundation: Prenatal detection of hemoglobinopathies in Cuba is performed on all pregnant women in Primary Health Care, through hemoglobin electrophoresis to identify high-risk couples. The program provides genetic counseling, molecular prenatal diagnosis and selective interruptions of affected fetuses, at the request of couples. Objective: Determine the type and frequency of hemoglobinopathies in Cuban pregnant women. Method: A descriptive, retrospective and cross-sectional study was carried out to determine the type of hemoglobinopathies in 1,342,917 pregnant women recruited over a period of ten years. The research method was hemoglobin electrophoresis in agarose gels at alkaline pH. Confirmation by electrophoresis of hemoglobin in agarose gel at acidic pH, both methods using the Hydrasys 2 equipment. Results: The overall frequency of pregnant women with hemoglobinopathies was 3.5%. Hemoglobinopathies were detected in 47,465 women; 38,698 with heterozygous S variant, 8,706 hemoglobin C variants and 158 other variants. 44,283 husbands with hemoglobinopathies were detected, 3,099 high-risk couples were detected, and 2,689 molecular prenatal diagnoses were performed. 522 affected fetuses were confirmed and 382 couples requested termination of pregnancy. The program reached 99.24% coverage in the country. Conclusions: The detection of hemoglobinopathies in pregnant women residing in Cuba allowed us to know the type of hemoglobinopathy and the frequency of abnormal hemoglobins and new variants, hence the interest in continuing the research program to prevent the appearance of severe forms of the disease.

Asociación del resultado auditivo final, en pacientes con hipoacusia súbita, a la respuesta a glucocorticoides in vitro / Association of the final hearing result, in patients with sudden hearing loss, to the response to glucocorticoids in vitro

Introducción: La hipoacusia súbita (HS) es poco frecuente y su etiopatogenia no está definida. La terapia con corticoides es de elección en base a recomendaciones de expertos por sus efectos teóricos y no en base a utilidad clínica demostrada. Objetivo: Evaluar si existe correlación entre el resultado auditivo final, de pacientes con HS tratados con corticoides, y la respuesta in vitro de sus leucocitos a corticoides, medida como diferencias en la expresión relativa de genes blanco del receptor de glucocorticoides. Material y Método: Estudio de casos (recuperación total) y controles (no recuperados) de pacientes con HS tratados con corticoides en el Hospital Clínico de la Universidad de Chile, durante 2017-2019. Se obtuvo DNA que fue almacenado en el Biobanco de Tejidos y Fluidos de la Universidad de Chile (BTUCH). Se purificaron y cultivaron leucocitos mononucleares de sangre periférica, expuestos in vitro a hidrocortisona. Se determinó la diferencia en la expresión relativa de genes blanco (IGFBP1, CAT, HSD17B12, APOA2), por Q-RTPCR, entre ambos grupos. Resultados: Se reclutaron 35 pacientes; se incluyeron para análisis 23: 11 casos y 12 controles, con edad promedio de 54,9 y 50,8 años respectivamente, distribución homogénea de sexo. No hubo diferencia estadísticamente significativa en la expresión relativa de los genes blanco, a la exposición in vitro a corticoides, entre ambos grupos. Conclusión: En nuestro estudio, modelo, y sistema de evaluación no se evidenciaron efectos de los corticoides. No podemos descartar que, con un número mayor de pacientes, otros genes blanco u otros protocolos de estudio podrían detectarse diferencias.

Introduction: Sudden hearing loss (SHL) is rare and its etiopathogenesis is still not clear. Corticosteroid therapy is of choice based on expert recommendations due to its theoretical effects and no based on proved clinical efficacy. Objectives: To assess whether there is a correlation between the final auditory outcome of patients with SHL treated with corticosteroids and the in vitro response of their leukocytes to corticosteroids, measured as differences in the relative expression of glucocorticoid receptor target genes. Material and Method: Case-control (total recovery and not recovered respectively) study of patients with SHL treated with corticosteroids at Clinical Hospital Universidad de Chile between 2017 and 2019. DNA was obtained and stored in the Biobanco de Tejidos y Fluidos de la Universidad de Chile (BTUCH). Peripheral blood mononuclear leukocytes were purified and cultured and then exposed to hydrocortisone. The difference in the relative expression of target genes (GFBP1, CAT, HSD17B12, APOA2), by Q-RTPCR was determined. Results: Thirty-five patients were recruited, 24 were included for the analysis: 11 cases and 12 controls, with and average age of 54.9 and 50.,8 years respectively, homogeneous sex distribution. There was no statistically significant difference in the relative expression of the target genes, upon in vitro exposure to corticosteroids, between both groups. Conclusion: In our study, model and evaluation system, no effects of corticosteroids were evidenced. With a larger number of patients, other target genes or other study protocols, we cannot rule out that differences could be detected.

COMMON HUB GENES AND DRUG CANDIDATES FOR DIABETIC KIDNEY DISEASE AND NON-ALCOHOLIC FATTY LIVER DISEASE: A COMPREHENSIVE BIOINFORMATIC STUDY

Diabetes mellitus (DM) is one of the most prevalent diseases responsible for worldwide morbidity and mortality. The kidney and liver are the most commonly affected organs resulting in diabetic kidney disease (DKD) and non-alcoholic fatty liver disease (NAFLD). However, pathophysiological mechanisms that may be common to both DKD and NAFLD have not been elaborated despite having a common underlying cause. This study aimed to identify the hub genes that are common to both DKD and NAFLD and explore the potential drugs for their treatment. Gene expression datasets for DKD and NAFLD from the gene expression omnibus database were analyzed to identify differentially expressed genes (DEGs). A functional enrichment analysis of the DEGs was done to reveal pathways important in the etiology of DKD and NAFLD. Protein-protein interaction (PPI) network was constructed and hub genes were identified. The hub genes were further analyzed to identify potentially viable drug candidates after screening. A total of 89 DEGs were found to be common between DKD and NAFLD. Functional enrichment of said DEGs found Ppar, FoxO signaling and hepatocellular carcinoma pathways to be most prevalent in DKD and NAFLD. From the PPI network, 32 common hub genes were identified. The hub genes were analyzed for interacting drugs. Finally, 9 drugs were identified as potential candidates for the treatment of both diseases. The hub genes identified can provide new insights into the common etiology of DKD and NAFLD. The potentially viable drugs may be repurposed for the treatment of both DKD and NAFLD.

Analysis of the differences in immune-related genes and immune cell subtypes in acute myocardial infarction

Acute myocardial infarction (AMI) continues to be a leading cause of death globally, with distinct immune cell dynamics in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) playing a critical role in disease progression and patient outcomes. Sample data for STEMI and NSTEMI were downloaded from the Sequence Read Archive (SRA) database (https://www.ncbi.nlm.nih.gov/sra). Differences and correlations of immune infiltrating cells were assessed by CIBERSORT. Differentially expressed genes (DEGs) were identified between STEMI and NSTEMI, followed by functional analysis. Immune-related DEGs were further identified. Some immune-related DEGs were selected to perform expression verification using real-time PCR. There was a significant difference in immune cells between STEMI and NSTEMI, including activated dendritic cells, memory CD4 T cells, mast cells, and CD8 T cells. A total of 229 DEGs were identified, with functions related to inflammatory regulation and drug metabolism. A total of 21 immune-related DEGs, which may play important roles in STEMI and NSTEMI, were identified. Among the 21 immune-related DEGs, genes like CCL18, NRP2, CXCR2, CXCL9, KIR2DL4, BPIFB1, and IL33 were significantly correlated with immune cells and had a tendency for differential expression between STEMI and NSTEMI patients. Our study reveals differences in the distribution of immune cell subsets between STEMI and NSTEMI, highlighting key immune-related genes and their association with immune cells, which may provide new insights into the treatment of AMI.

Screening and bioinformatics analysis of key autophagy-related genes in alcoholic hepatitis / 器官移植

Objective To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH. Methods Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice. Results Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group. Conclusions SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics / 中华创伤杂志(英文版)

PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Research progress on the association between biorhythm disorders and cardiovascular metabolic risk in adolescents and possible mechanisms / 中国学校卫生

Abstract@#Adolescence is a unique transitional period from childhood to adulthood, during which behavioral habits and physiological cycles undergo significant changes, and biorhythms are vulnerable to be disrupted. Meanwhile, due to increased rates of overweight and obesity, cardiovascular metabolic risk significantly increases during adolescence. The article reviews the prevalence, correlation, and potential epigenetic regulatory mechanisms of biorhythm disorders and adolescent cardiovascular metabolic health, providing a theoretical basis for regulating biorhythm to promote adolescent cardiovascular metabolic health.

Bioinformatics analysis based on pelvic organ prolapse related aging genes of GEO Database and LASSO regression algorithm / 吉林大学学报(医学版)

Objective:To screen the aging genes closely associated with pelvic organ prolapse(POP)by bioinformatics techniques,and to clarify the potential clinical significance and value of key genes.Methods:Gene Expression Omnibus(GEO)Database was used to download the datasets GSE53868 and GSE151188 for POP-related genes with the keyword"pelvic organ prolapse".The aging-related genes were obtained from Aging Atlas,CellAge,and the Human Ageing Genomic Resources(HAGR)Databases;the intersection of genes related with POP in two groups provided a list of differentially expressed genes(DEGs)associated with aging in POP;gene Set Enrichment Analysis(GSEA)was conducted with R software version 4.2.1;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis of DEGs were conducted by the Database for Annotation,Visualization and Integrated Discovery(DAVID);the protein-protein interaction(PPI)network was constructed with Cytoscape 3.9.1 software;the top 10 Hub genes were selected by cytoHubba plugin;the infiltration of 22 types of immune cells in the patients in POP group and control group was analyzed by CIBERSORT deconvolution method using R software;the key genes were further screened by LASSO regression algorithm;the correlation and diagnostic efficacy between key genes and immune cell infiltration were analyzed.Results:From the Aging Atlas,CellAge,and HAGR Databases,724 aging-related genes were identified.Intersection with the POP expression profile yielded an aging gene expression matrix related to POP containing 624 genes,and 29 POP-related DEGs were identified after differential analysis,including 2 upregulated genes and 27 downregulated genes.The GSEA results showed that the upregulated pathways were mainly related to diabetes and cellular senescence,whereas the downregulated pathways included Alzheimer's disease and hypoxia-inducible factor-1(HIF-1)signaling pathways.The GO functional enrichment analysis mainly enriched in the biological processes such as the response of the cells to lipopolysaccharide,inflammatory response,and negative regulation of cell proliferation.The KEGG signaling pathway enrichment analysis mainly enriched in interleukin-17(IL-17),tumor necrosis factor(TNF),and nuclear factor-kappa B(NF-κB)signaling pathways.The PPI network analysis got 10 Hub genes including interleukin-6(IL-6),interleukin-1B(IL-1B),prostaglandin-endoperoxide synthase 2(PTGS2),and NF-kappa-B inhibitor alpha(NFKBIA).The CIBERSORT deconvolution method results showed a relatively higher infiltration proportion of neutrophils and activated mast cells in the patients in POP group,the activated mast cells had a positive correlation with most of the DEGs(r>0.5)and the macrophages had a significant positive correlation with IL-1B(r>0.6).The key genes Jun D proto-oncogene(JUND),Snail homolog 1(SNAI1),amphiregulin(AREG),Lamin A/C(LMNA),and superoxide dismutase 2(SOD2)selected by LASSO regression analysis had high diagnostic efficacies,and the area under receiver operating characteristic curve(ROC)(AUC)were all greater than 0.75.Conclusion:During the aging process,the genes such as JUND,SNAI1,AREG,LMNA,and SOD2 may participate in the pathophysiology of POP through various pathways,including inflammation-related pathways,transcription regulation,and affecting collagen secretion and metabolism,thereby influence the connective tissue support function and promote the occurrence and development of POP.

Clinical features of CpG island methylation in colon cancer and its prognostic significance in dMMR colon cancer / 国际外科学杂志

Objective:To investigate the clinical characteristics and prognosis of CpG island methylator phenotype (CIMP+ ) colon cancer, and the significance of CIMP status in the diagnosis and prognosis prediction in defective mismatch repair (dMMR) colon cancer.Methods:The keywords "colorectal cancer" "patient" and "CpG Island Methylator Phenotype" were used to search the Gene Expression Omnibus (GEO) database, and the GSE39582 was obtained, which included the clinical data of 585 patients with colorectal cancer and the sequencing data of the whole transcriptome of the tumor tissues. After excluding 72 cases with missing CIMP values, 513 cases were included for further analysis, including 278 males and 235 females, with a mean age of (67±13) years. According to the CIMP status, they were divided into CIMP+ group ( n=93) and CIMP-group ( n=420), then compare the differences in clinical characteristics, the Kaplan-Meier survival curves were plotted to compare the overall survival and disease-free survival; 71 dMMR cases were divided into CIMP+ group ( n=43) and CIMP-group ( n=28), and the K-M curves were plotted to analyze the differences in overall survival (OS) and disease free survival (DFS). Comparisons between groups were performed by t-test, χ2 test or Mann-Whitney U nonparametric test, and the difference in survival curves was tested by Long-rank test. Results:Patients in the CIMP+ group were significantly older than those in the CIMP-group [(70.84±12.60) years vs (66.21±13.08) years, t=3.18, P=0.002]. Right colon tumors originating from the CIMP+ molecular pathway were 9.3 times more likely to be CIMP+ than those of the left colon cancers ( OR=9.3, 95% CI: 5.2-17.9). BRAF mutant colon cancer originating from CIMP+ was 215.2 times more common than BRAF wild-type colon cancer originating with CIMP+ ( OR=215.2, 95% CI: 53.2-1906.7); and patients with dMMR colon cancer originated 12.8 times more common than patients with pMMR ( OR=12.8, 95% CI: 7.0-23.9). The difference between the CIMP+ and CIMP-groups was not statistically significant in terms of overall survival and disease-free survival ( P=0.590, 0.220). In the dMMR colon cancer subgroup, CIMP status did not correlate with patients′ overall survival and disease-free survival ( P>0.05). Conclusions:CIMP+ colon cancer patients were mostly of advanced age, with tumors originating from the right colon, mostly combined with BRAF gene mutations, and manifested as mismatch repair-deficient colon cancers. CIMP status had no correlation with TNM stage and survival of colon cancers patients. There was no significant difference in the survival between dMMR colon cancers caused by CIMP+ and those caused by MMR gene mutations.

Study on the Difference of Gene Expression Between Left and Right Colon Cancer and the Mechanism of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba Based on TCGA / 广州中医药大学学报

Abstact:Objective To investigate the gene expression differences between left-sided colon cancer and right-sided colon cancer and the mechanism differences between the colorectal cancer core drug pairs of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba acting on left-sided and right-sided colon cancer.Methods The transcriptome data of 134 patients with left-sided colon cancer and 194 patients with right-sided colon cancer from The Cancer Genome Atlas(TCGA)were downloaded,and the R software was applied to realize the differential gene analysis of the two groups and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway;the BATMAN-TCM database was used to obtain the active ingredients and targets of the drug pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,and based on the different genes of the left-and right-sided colon cancers,KEGG enrichment analysis of the drug pair-left/right-sided colon cancers was performed respectively,and the protein-protein-interaction(PPI)network was constructed to compare the differences of the biosignaling pathways enriched by the drug pairs for the treatment of left-and right-sided colon cancers,as well as the differences of the key target points.Results There were 6 051 differentially expressed genes common to left-and right-sided colon cancers relative to normal paracancerous tissues,1958 differentially expressed genes specific to left-sided colon cancer,and 1739 differentially expressed genes specific to right-sided colon cancer;14 KEGG-enriched pathways specific to left-sided colon cancer,and 23 KEGG-enriched pathways specific to right-sided colon cancer.There were 85 active compounds in the drug-pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,corresponding to a total of 469 targets.The drug-pair-left-sided colon cancer targets were enriched in 10 KEGG signaling pathways,with the key targets being DRD2,CACNA1C,HTR3A,COMT,and TH;and the drug-pair-right-sided colon cancer targets were enriched in 1 KEGG signaling pathway,with the core targets being HTR3A,DRD2 TH,AGT,GRIN2B.Conclusion There are gene expression differences between left-and right-sided colon cancers:left-sided colon cancer is associated with abnormal immune function,abnormal AMPK signaling pathway and other mechanisms,and right-sided colon cancer is associated with neutrophil extracellular trap formation,alcoholism,abnormal Hippo signaling pathway and other mechanisms.In addition to regulating cell cycle and essential amino acid metabolism and other mechanisms,Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba drug pairs have specific effects on regulating the intestinal endocrine function of the left-sided colon cancer,inhibiting inflammatory response of the right-sided colon cancer,and may also have mood-regulating effects on patients with colon cancer.

Qizhi Zhoufei Granule Alleviate Chronic Obstructive Pulmonary Disease by Regulating Th1/Th2 Immunologic Balance Through Notch Signaling Pathway / 世界科学技术-中医药现代化

Objective To investigate the role of homologous genes absent from the wings of drosophila melanogaster(Notch)signaling pathway in the imbalance of helper T cells 1(Th1)and helper T cells 2(Th2)and the intervention mechanism of Qizhi Zhoufei Granule in chronic obstructive pulmonary disease(COPD).Methods Ten of seventy Wistar rats were selected as the blank control group,and the other rats were established by cigarette smoking combined(CS)with tracheal infusion of lipopolysaccharide(LPS).The COPD model was established by randomly selecting 3 rats in the control group and the model group to verify the success of the model.At the end of modeling,gavage administration was performed.The rats in the model group were randomly divided into model control group,positive control group(67.5 μg·kg-1)and Qizhi Zhoufei Granule high,medium and low treatment group(3.24,1.62,0.81 g·kg-1).Each group was treated with normal saline,dexamethasone acetate suspension and Qizhi Zhoufei Granule suspension at high,medium and low doses.The rats in the blank control group were given the same volume of normal saline as the model control group.After modeling with 28 days and treatment with 28 days,peak inspiratory flow(PIF)and peak expiratory flow(PEF)were detected by the animal lung function test system.Rats were killed to extract lungs,spleen,serum and bronchoalveolar lavage fluid(BALF),hematoxylin-eosin(HE)staining was used to evaluate the pathological changes of lung tissues.The level of tumor necrosis factor-α(TNF-α)in serum and BALF was determined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect Th1/Th2 cells in spleen.Immunohistochemistry(IHC)and western blot were used to detect Notch1,Hes1 and Hey1 protein levels in lung tissues.Real-time fluorescence quantitative polymerase chain reaction(Real-Time PCR)was used to detect Notch1,Hes1 and Hey1 gene expression levels in lung tissues.Result Compared with the blank control group,the lung function of the model control group was significantly decreased(P<0.05),inflammatory cell infiltration and bronchial structure destruction occurred in the lung tissue,TNF-α content in serum and BALF increased significantly(P<0.05),the percentage of spleen Th1 cells was significantly decreased(P<0.05),and the percentage of Th2 cells was significantly increased(P<0.05),the protein and mRNA expressions of Notch1,Hes1 and Hey1 in lung tissues were significantly increased(P<0.05),the differences were statistically significant;Compared with the model control group,the lung function of rats in each administration group was significantly increased(P<0.05),the pathological injury of lung tissue was alleviated,TNF-α content in serum and BALF decreased significantly(P<0.05),the percentage of spleen Th1 cells was significantly increased(P<0.05),the percentage of Th2 cells was significantly decreased(P<0.05),the lung tissue of Notch1,Hes1,Hey1 protein and mRNA expression were significantly decreased(P<0.05),the differences were statistically significant.Conclusion Qizhi Zhoufei Granule regulate Th1/Th2 balance by inhibiting Notch signaling pathway,thereby improving pulmonary function and pathological injury,and affecting immune function in COPD rats.

Screening of IL-3 and IL-3+SCF Induce Differentially Expressed Genes and Signaling Pathways in Bone Marrow-derived Mast Cells Based on Bioinformatics / 现代检验医学杂志

Objective To identify the differentially expressed genes and pathways of bone marrow-derived mast cells(BMMCs)of mice induced by IL-3 and IL-3+stem cell factor(SCF)using bioinformatics analysis,which may provide a foundation for in vitro culture and functional study of mast cells(MC).Methods The matrix data of GSE35332 dataset in IL-3 and IL-3+SCF induced BMMCs was downloaded from the GEO database,and the R software was applied to screen differentially expressed genes(DEGs).The gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of EDGs were performed based on the online tool DAVID database.The protein interaction network was constructed by STRING database and hub genes were screened through MCODE plugin of the Cytoscape software.Results The GSE35332 data set was analyzed by R software,and 1 339 DEGs were screened,including 723 up-regulated genes and 616 down-regulated genes.A total of 6 hub genes were screened through the MCODE plugin of Cytoscape software,namely Psmd8,Psmd6,Psmd14,Psmc4,Psma6 and Psma3.GO and KEGG analysis showed that the hub genes were concentrated in proteolysis,antigen processing and presentation of exogenous peptide antigen via MHC class I,proteasome-mediated ubiquitin-dependent protein catabolism process,and Epstein-Barr virus infection.Conclusion This study found that there were significant differences in BMMCs gene expression profiles in mice induced by two modes and 6 hub genes participated in ubiquitin-dependent protein decomposition process through bioinformatics based on the GEO database,providing help for further research on MC vitro culture and function.