Mecanismos compensatorios a nivel sistémico en pacientes con tronco arterial persistente / Systemic Compensatory Mechanisms in Patients with Persistent Truncus Arteriosus

Resumen Introducción: El tronco arterial persistente es una rara malformación cardíaca congénita que provoca diversas complicaciones en el sistema cardiovascular. Se caracteriza por la presencia de un tabique ventricular defectuoso, una única válvula troncal y un tronco arterial común entre la arteria pulmonar y aorta, conllevando a una mezcla entre la sangre arterial y venosa, debido a un cortocircuito cardíaco bidireccional predominante de izquierda a derecha que compromete el suministro de flujo sanguíneo, nutrientes y oxigenación sistémica. Las manifestaciones clínicas incluyen desaturación con cianosis, hipoxemia, taquicardia, taquipnea, alteraciones en la contractilidad cardíaca, pulsos distales anómalos, pérdida de peso, fatiga y hepatomegalia. Objetivo: El propósito de esta investigación es establecer hipótesis sobre los diversos mecanismos compensatorios que se activan a nivel sistémico para contrarrestar los efectos de esta malformación. Reflexión: Se sugiere que se producen respuestas biomoleculares similares en los sistemas cardiovascular, pulmonar y renal, reduciendo la producción de óxido nítrico y provocando respuestas vasoconstrictoras. A nivel hepático, se generan factores de crecimiento y se inician procesos de angiogénesis para aumentar la perfusión sanguínea. En el cerebro, se activan enzimas para incrementar el flujo sanguíneo y proporcionar oxígeno y nutrientes esenciales. Conclusión: A pesar de estos mecanismos compensatorios, no logran contrarrestar por completo las manifestaciones clínicas, conduciendo a una serie de problemas de salud, como hipertensión pulmonar, insuficiencia cardíaca, hepatomegalia, hipoperfusión de órganos y déficits neurológicos. Estos factores convergen para generar una compleja condición cardíaca que desencadena respuestas adaptativas en el cuerpo que terminan siendo una afección médica desafiante y potencialmente grave.

Abstract Introduction: Persistent truncus arteriosus is a rare congenital cardiac malformation that causes various complications in the cardiovascular system. It is characterized by the presence of a defective ventricular septum, a single truncal valve and a common truncus arteriosus between the pulmonary artery and aorta, leading to a mixture between arterial and venous blood, due to a predominantly left-to-right bidirectional cardiac shunt that compromises the supply of blood flow, nutrients, and systemic oxygenation. Clinical manifestations include desaturation with cyanosis, hypoxemia, tachycardia, tachypnea, alterations in cardiac contractility, abnormal distal pulses, weight loss, fatigue, and hepatomegaly. Aim: The purpose of this research is to establish hypotheses about the various compensatory mechanisms that are activated at a systemic level to counteract the effects of this malformation. Reflection: It is suggested that similar biomolecular responses occur in the cardiovascular, pulmonary, and renal systems, reducing nitric oxide production and causing vasoconstrictive responses. At the liver level, growth factors are generated and angiogenesis processes are initiated to increase blood perfusion. In the brain, enzymes are activated to increase blood flow and provide oxygen and essential nutrients. Conclusion: Despite these compensatory mechanisms, they fail to completely counteract the clinical manifestations, leading to a series of health problems such as pulmonary hypertension, heart failure, hepatomegaly, organ hypoperfusion, and neurological deficits. These factors converge to generate a complex cardiac condition that triggers adaptive responses in the body that end up being a challenging and potentially serious medical condition.

Clinical significance and different strategies for re-elevation of plasma EBV-DNA during treatment in pediatric EBV-associated hemophagocytic lymphohistiocytosis

Abstract Objective Monitoring the disease status of Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH) patients is crucial. This study aimed to investigate the different strategies and outcomes of patients with EBV-HLH and re-elevated EBV-DNA. Method A retrospective analysis was conducted on 20 patients diagnosed with EBV-HLH. Clinical features, laboratory tests, treatments, plasma EBV-DNA levels, and outcomes were assessed. Three cases were highlighted for detailed analysis. Results Nine of the 20 patients had a re-elevation of EBV-DNA during treatment, and 55.5 % (5/9) experienced relapses. Patients with persistently positive plasma EBV-DNA (n = 4) and those with re-elevated EBV-DNA after conversion (n = 9) showed a significantly higher relapse rate compared to those with persistently negative EBV-HLH (n = 7) (p < 0.05). Among the highlighted cases, Case 1 exhibited plasma EBV-DNA re-elevation after four weeks of treatment without relapse, maintaining stability with the original treatment regimen, and eventually, his plasma EBV-DNA turned negative. In Case 2, plasma EBV-DNA was elevated again with a recurrence of HLH after L-DEP. Consequently, she underwent allogeneic hematopoietic stem cell transplantation and eventually achieved complete remission (CR) with negative plasma EBV-DNA. Case 3 experienced plasma EBV-DNA re-elevation after L-DEP but remained in CR, discontinuing chemotherapy without relapse. Conclusion The re-elevation of plasma EBV-DNA during EBV-HLH treatment poses challenges in determining disease status and treatment strategies. Optimal management decisions require a combination of the level of elevated EBV-DNA, the intensity of hyperinflammation, and the patient's immune function.

Comportamiento alimentario de Aedes aegypti en brotes de dengue de dos zonas rurales del Perú durante el ciclón Yaku y El Niño Global del 2023 / Aedes aegypti feeding behavior during dengue outbreaks in two rural areas of Peru during the Yaku cyclone and El Niño phenomenon of 2023

RESUMEN Objetivos. Determinar la alimentación del Aedes aegypti en brotes de dengue de dos zonas rurales del Perú durante el ciclón Yaku y El Niño Global del 2023. Material y métodos. Se analizaron ocho muestras de sangre (8 pooles) obtenidas del abdomen de 80 especímenes Aedes aegypti capturados en los distritos rurales de Querecotillo y Marcavelica durante brotes de dengue acontecidos en el ciclón Yaku y en El Niño Global. Se extrajo ADN de las muestras analizadas, se llevó a cabo una PCR dirigida al gen CytB como marcador genético y los productos PCR fueron digeridos enzimáticamente con las restrictasas Hae III y Mwo I. Los productos PCR-RFLP fueron visualizados por electroforesis en gel de agarosa al 4%. Resultados. Se obtuvo ADN de todas las muestras y como producto PCR un amplicón de 358 pb. Así mismo, el único RFLP en Hae III observado fue el de Homo sapiens sapiens (233 y 125 pb). No se observó RFLP en Hae III de Gallus gallus y RFLP en Mwo I de Canis familiaris y Mus musculus. Conclusión. En brotes de dengue de zonas rurales, durante el ciclón Yaku y en El Niño Global, el Aedes aegypti presentó un comportamiento alimenticio antropofílico conservado.

ABSTRACT Objective. To determine the feeding behavior of Aedes aegypti in dengue outbreaks in two rural areas of Peru during the Yaku cyclone and El Niño phenomenon of 2023. Material and methods. Eight blood samples (8 pools) were obtained from the abdomen of 80 Aedes aegypti specimens captured in the rural districts of Querecotillo and Marcavelica during the Yaku cyclone and El Niño dengue outbreaks. DNA was extracted from the analyzed samples, then a PCR was directed at the CytB gene as a genetic marker and the PCR products were enzymatically digested with the restrictases Hae III and Mwo I. The PCR-RFLP products were visualized by agarose gel electrophoresis at 4%. Results. DNA was obtained from all samples and a 358 bp amplicon was obtained as a PCR product. Likewise, the only RFLP found in Hae III was from Homo sapiens sapiens (233 and 125 bp). RFLP was not found in Hae III of Gallus gallus and RFLP in Mwo I of Canis familiaris and Mus musculus. Conclusion. Aedes aegypti showed conserved anthropophilic feeding behavior in dengue outbreaks in rural areas during the Yaku cyclone and El Niño.

Infective keratitis: a concise overview of the clinical characteristics and treatment of keratitis caused by microbial agents

The following document provides an overview of microbial keratitis, a well-known sight-threatening inflammation of the cornea that progresses to the corneal ulcer. Sometimes, such infection is difficult to identify and cure due to the involvement of multiple pathogens implicated in the specific disorders because of similar symptoms and immunological responses. Instead of fungi and protozoa, viruses and bacteria are the most prevalent pathogens that cause microbial keratitis. A virus contains protein-encased genetic material and may infect any living creature, including bacteria and fungi, by replicating inside the host's cell and infecting neighbouring cells. Bacteria are complicated pathogens that may thrive in any media and cause harm to host cells, often through the production of toxins. Fungi are far more difficult; they spread quickly and can cause harm to several organs at the same time if the immune system is compromised. Protozas are found freely in the environment and once invade the cornea, divide quickly and become difficult to identify as well as treat, because of their involvement or in conjunction with polymicrobials. These microbes show common symptoms after invading the cornea although; their common diagnostic procedures show different results to trace out their existence in the tissue. Up to some extent, specific treatment can cure the disease with certain conditions according to a load of microbes, therefore visual status gets hampered, otherwise total loss of the eye takes place due to the endophthalmitis.

Comparison of Hybribio-H13 and Hybrid Capture® 2 human papillomavirus tests for detection of CIN2+ and CIN3+ / Comparación de las pruebas para el virus del papiloma humano Hybribio-H13 y Hybrid Capture® 2 para la detección de NIC2+ y NIC3+

Introduction. Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. Objective. To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). Materials and methods. Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. Results. Therelative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT < 0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. Conclusion. The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.

Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT < 0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.

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.

Importancia biológica de los telómeros / Biological importance of telomeres

Se exponen los hallazgos históricos y la importancia biológica de los telómeros en la vida celular y en los aspectos genéticos del ADN humano. (AU)

The discovery and the biological importance of the telomeres are exposed. (AU)

Evaluating the reliability of DNA Barcoding for Central American Pacific shallow water echinoderms identification: a molecular taxonomy and database accuracy analysis / Evaluando la fiabilidad del Código de Barras de ADN para la identificación de equinodermos en aguas poco profundas del Pacífico de América Central: un análisis de taxonomía molecular y precisión de bases de datos

Abstract Introduction: Molecular divergence thresholds have been proposed to distinguish recently separated evolutive units, often displaying more accurate putative species assignments in taxonomic research compared to traditional morphological approaches. This makes DNA barcoding an attractive identification tool for a variety of marine invertebrates, especially for cryptic species complexes. Although GenBank and the Barcode of Life Data System (BOLD) are the major sequence repositories worldwide, very few have tested their performance in the identification of echinoderm sequences. Objective: We use COI echinoderm sequences from local samples and the molecular identification platforms from GenBank and BOLD, in order to test their accuracy and reliability in the DNA barcoding identification for Central American shallow water echinoderms, at genus and species level. Methods: We conducted sampling, tissue extraction, COI amplification, sequencing, and taxonomic identification for 475 specimens. The 348 obtained sequences were individually enquired with BLAST in GenBank as well as using the Identification System (IDS) in BOLD. Query sequences were classified depending on the best match result. McNemar's chi-squared, Kruskal-Wallis's and Mann-Whitney's U tests were performed to prove differences between the results from both databases. Additionally, we recorded an updated list of species reported for the shallow waters of the Central American Pacific. Results: We found 324 echinoderm species reported for Central American Pacific shallow waters. Only 118 and 110 were present in GenBank and BOLD databases respectively. We proposed 325 solved morphology-based identities and 21 provisional identifications in 50 putative taxa. GenBank retrieved 348 molecular-based identifications in 58 species, including twelve provisional identifications in tree taxa. BOLD recovered 170 COI identifications in 23 species with one provisional identification. Nevertheless, 178 sequences retrieved unmatched terms (in 34 morphology-based taxa). Only 86 sequences (25 %) were retrieved as correct identifications and 128 (37 %) as identification errors in both platforms. We include 84 sequences for eleven species not represented in GenBank and 65 sequences for ten species in BOLD Echinoderm COI databases. The identification accuracy using BLAST (175 correct and 152 incorrect identifications) was greater than with IDS engine (110 correct and 218 identification errors), therefore GenBank outperforms BOLD (Kruskal-Wallis = 41.625, df = 1, p < 0.001). Conclusions: Additional echinoderm sample references are needed to improve the utility of the evaluated DNA barcoding identification tools. Identification discordances in both databases may obey specific parameters used in each search algorithm engine and the available sequences. We recommend the use of barcoding as a complementary identification source for Central American Pacific shallow water echinoderm species.

Resumen Introducción: Se han propuesto los umbrales de divergencia molecular para distinguir unidades evolutivas recientemente separadas, que a menudo muestran asignaciones de especies putativas más precisas en la investigación taxonómica en comparación con los enfoques morfológicos tradicionales. Esto hace que los Códigos de Barras de ADN sean una herramienta de identificación atractiva para una variedad de invertebrados marinos, especialmente para complejos de especies crípticas. Aunque GenBank y Barcode of Life Data System (BOLD) son los principales repositorios de secuencias en todo el mundo, muy pocos han probado su desempeño en la identificación de secuencias de equinodermos. Objetivo: Utilizamos secuencias de equinodermos COI de muestras locales y las plataformas de identificación molecular de GenBank y BOLD, para probar su precisión y confiabilidad en la implementación de códigos de barras de ADN para equinodermos de aguas someras de Centroamérica, a nivel de género y especie. Métodos: Realizamos muestreo, extracción de tejido, amplificación de COI, secuenciación e identificación taxonómica de 475 especímenes. Las 348 secuencias obtenidas fueron consultadas individualmente con BLAST en GenBank así como utilizando el Sistema de Identificación (IDS) en BOLD. Las secuencias consultadas se clasificaron según el mejor resultado de coincidencia. Se realizaron las pruebas chi-cuadrado de McNemar, Kruskal-Wallis y U de Mann-Whitney para comprobar diferencias entre los resultados de ambas bases de datos. Además, registramos una lista actualizada de especies reportadas para las aguas someras del Pacífico Centroamericano. Resultados: Encontramos 324 especies de equinodermos reportadas para aguas someras (< 200 m) del Pacífico centroamericano. Sólo 118 y 110 estaban presentes en las bases de datos GenBank y BOLD respectivamente. Propusimos 325 identidades resueltas basadas en morfología y 21 identificaciones provisionales en 50 taxones putativos. GenBank recuperó 348 identificaciones de base molecular en 58 especies, incluidas doce identificaciones provisionales en tres taxones. BOLD recuperó 170 identificaciones de COI en 23 especies con una identificación provisional. Sin embargo, 178 secuencias recuperaron términos no coincidentes (en 34 taxones basados en morfología). Sólo 86 secuencias (25 %) se recuperaron como identificaciones correctas y 128 (37 %) como errores de identificación en ambas plataformas. Incluimos 84 secuencias para once especies no representadas en GenBank y 65 secuencias para diez especies ausentes en las bases de datos BOLD Echinoderm COI. La precisión de la identificación usando BLAST (175 identificaciones correctas y 152 incorrectas) fue mayor que con el motor IDS (110 correctas y 218 errores de identificación), por lo tanto, GenBank supera a BOLD (Kruskal-Wallis = 41.625, df = 1, p < 0.001). Conclusiones: Se necesitan muestras adicionales de equinodermos de referencia para mejorar la utilidad de las herramientas de identificación de códigos de barras de ADN evaluadas. Las discordancias de identificación en ambas bases de datos pueden obedecer a parámetros específicos utilizados en cada algoritmo de búsqueda y a las secuencias disponibles. Recomendamos el uso de códigos de barras como fuente de identificación complementaria para las especies de equinodermos de aguas someras del Pacífico centroamericano.

Recent molecular techniques to strengthen ecological studies in echinoderms / Técnicas moleculares recientes que fortalecen los estudios ecológicos de equinodermos

Abstract Introduction: Echinoderms, an integral component of marine ecosystems worldwide, have captivated scientific interest for centuries. Despite this longstanding attention, comprehending key facets such as trophic relationships, diet composition, and host-microbiota relationships still represents a challenge using traditional techniques. Recent years, however, have witnessed a transformative shift, thanks to the emergence of advanced molecular techniques, offering new approaches to strengthen ecological studies in echinoderms. Objective: Explore how recent advancements in molecular tools have impacted ecological research on echinoderms. Specifically, we aim to investigate the potential of these tools to shed light on trophic interactions, diet composition, and the characterization of gut microbial communities in these organisms. Methods: Available literature was used to clarify how novel molecular techniques can improve ecological studies. The focus is diet, trophic relationships, and gut microbiota. Results: Traditionally, studies of stomach contents using compound microscopy have provided an idea of ingested material; nevertheless, sometimes a simple magnified visualization of dietary content does not allow exhaustive identification of the entire food spectrum, as it is limited due to the rapid digestion and maceration of food items within the echinoderm's digestive tract. The use of DNA-metabarcoding, targeting specific DNA regions, such as the mitochondrial COI gene, has allowed us to enhance the accuracy and precision of diet characterization by enabling the identification of prey items down to the species or even genetic variant level, providing valuable insights into specific dietary preferences. Another approach is the use of stable isotopes, particularly carbon and nitrogen, which provide a powerful tool to trace the origin and flow of nutrients through food webs. By analyzing the isotopic signatures in muscular tissues and food items, we can discern the sources of their primary food items and gain insights into their trophic position within the ecosystem. Lastly, a third new technique used to elucidate the characterization of the prokaryotic community is 16S rRNA sequencing. This method allows us to explore the composition and dynamics of the digestive tract microbial communities. Conclusions: This is a promising era for ecological research on echinoderms, where advances of molecular tools have enabled an unprecedented level of detail, resolving longstanding challenges in comprehending their trophic interactions, diet composition, and host-microbiota relationships, and opening new avenues of investigation in ecological studies.

Resumen Introducción: Los equinodermos, un componente integral de los ecosistemas marinos en todo el mundo, han captado el interés científico durante siglos. A pesar de esta prolongada atención, el comprender facetas clave como las relaciones tróficas, la composición de la dieta y las relaciones huésped-microbiota todavía representa un desafío utilizando técnicas tradicionales. Sin embargo, los últimos años han sido testigos de un cambio transformador, gracias a la aparición de técnicas moleculares avanzadas, que ofrecen nuevos enfoques para fortalecer los estudios ecológicos en equinodermos. Objetivo: Explorar cómo los avances recientes en herramientas moleculares han impactado la investigación ecológica sobre equinodermos. Específicamente, nuestro objetivo es investigar el potencial de estas herramientas para arrojar luz sobre las interacciones tróficas, la composición de la dieta y la caracterización de las comunidades microbianas intestinales en estos organismos. Métodos: Se utilizó la literatura disponible para aclarar cómo las nuevas técnicas moleculares pueden mejorar los estudios ecológicos. La atención se centra en la dieta, las relaciones tróficas y la microbiota intestinal. Resultados: Tradicionalmente, los estudios del contenido estomacal mediante microscopía compuesta han proporcionado una idea del material ingerido; Sin embargo, a veces una simple visualización ampliada del contenido dietético no permite una identificación exhaustiva de todo el espectro alimentario, ya que está limitado debido a la rápida digestión y maceración de los alimentos dentro del tracto digestivo del equinodermo. El uso de metabarcoding de ADN, dirigidos a regiones específicas del ADN, como el gen COI mitocondrial, nos ha permitido mejorar la exactitud y precisión de la caracterización de la dieta al permitir la identificación de presas hasta el nivel de especie o incluso de variante genética, lo que proporciona valiosos resultados sobre preferencias dietéticas específicas. Otro enfoque es el uso de isótopos estables, en particular carbono y nitrógeno, que proporcionan una poderosa herramienta para rastrear el origen y el flujo de nutrientes a través de las redes alimentarias. Al analizar las firmas isotópicas en los tejidos musculares y los alimentos, podemos discernir las fuentes de sus alimentos primarios y obtener información sobre su posición trófica dentro del ecosistema. Por último, una tercera técnica nueva utilizada para dilucidar la caracterización de la comunidad procariótica es la secuenciación del ARNr 16S. Este método nos permite explorar la composición y dinámica de las comunidades microbianas del tracto digestivo. Conclusiones: Esta es una era prometedora para la investigación ecológica sobre equinodermos, donde los avances de las herramientas moleculares han permitido un nivel de detalle sin precedentes, resolviendo desafíos de larga data en la comprensión de sus interacciones tróficas, composición de la dieta y relaciones huésped-microbiota, y abriendo nuevas vías de investigación. en estudios ecológicos.

Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations

Immature hematopoietic progenitors are a constant source for renewal of hemocyte populations and the basic component of the tissue and cell repair apparatus. A unique property of these cells of internalizing extracellular double-stranded DNA has been previously shown. The leukostimulatory effect demonstrated in our pioneering studies was considered to be due to the feature of this cell. In the present research, we have analyzed the effects of DNA genome reconstructor preparation (DNAgr), DNAmix, and human recombinant angiogenin on both hematopoietic stem cells and multipotent progenitors. Treatment with bone marrow cells of experimental mice with these preparations stimulates colony formation by hematopoietic stem cells and proliferation of multipotent descendants. The main lineage responsible for this is the granulocyte-macrophage hematopoietic lineage. Using fluorescent microscopy as well as FACS assay, co-localization of primitive c-Kit- and Sca-1-positive progenitors and the TAMRA-labeled double-stranded DNA has been shown. Human recombinant angiogenin was used as a reference agent. Cells with specific markers were quantified in intact bone marrow and colonies grown in the presence of inducers. Quantitative analysis revealed that a total of 14,000 fragment copies of 500 bp, which is 0.2% of the haploid genome, can be delivered into early progenitors. Extracellular double-stranded DNA fragments stimulated the colony formation in early hematopoietic progenitors from the bone marrow, which assumed their effect on cells in G0. The observed number of Sca1+/c-Kit+ cells in colonies testifies to the possibility of both symmetrical and asymmetrical division of the initial hematopoietic stem cell and its progeny.

La importancia de evaluar el daño al DNA / The Importance of Assessing DNA Damage

Resumen Se calcula que el cuerpo humano está conformado por billones de células, las cuales sufren cientos de miles de lesiones al día en su DNA. Aunque el DNA no es la única biomolécula que sufre daños, su importancia radica en que es la única que no puede ser sustituida por la célula, así que, cuando esta sufre daños, la célula debe repararlos, tolerarlos o, en el caso extremo, activar las vías que la llevarán a la muerte, ya que lo importante es mantener la integridad celular y la homeostasis del organismo. Hay miles de agentes que pueden dañar al DNA, algunos los produce la misma célula y se les denomina 'agentes endógenos', mientras que otros son agentes externos y se les conoce como 'agentes exógenos'. La célula no puede evitar el daño causado por los agentes endógenos, ya que son productos de la actividad metabólica, por ejemplo; así que, cuando suceden se activan de forma inmediata los mecanismos celulares para mitigarlos. Lo mismo pasa con los daños causados por agentes exógenos, ya que la célula hará todo lo posible por disminuir los efectos adversos que pueden causar. El problema se pone de manifiesto cuando la célula no puede reparar los daños o los repara mal o son tantos que los mecanismos de reparación se ven rebasados, es entonces cuando el daño permanece en el DNA y se genera un estado de inestabilidad cromosómica que puede conducir a la célula a la disfunción y a la malignización. Este estado de inestabilidad cromosómica se puede ver reflejado en el aumento de rompimientos de DNA o de micronúcleos en las células expuestas, lo que se puede cuantificar por medio de métodos especiales como el 'Ensayo Cometa' y el 'Ensayo de Micronúcleos', ya que identificar el daño en el DNA es una forma de evaluar el potencial tóxico que tienen los agentes a los que están expuestas las poblaciones, permite conocer los mecanismos de acción que tienen y, además, ayuda a comprender los factores que influyen en el detrimento de la salud poblacional.

Abstract It is estimated that the human body is made of trillions of cells, which suffer hundreds of thousands of DNA lesions every day. Although DNA is not the only biomolecule that suffers damage, its importance lies in the fact that it is the only biomolecule that cannot be replaced by the cell, so when it suffers damage, the cell must repair it, tolerate or, in a extreme case, activate pathways that will lead to death, since the objective is to maintain cell integrity and the homeostasis of the organism.There are thousands of agents that can damage DNA, some are produced by the cell and are called 'endogenous, while others are external agents and are known as 'exogenous. The cell cannot avoid the damage caused by endogenous agents, since they are products of its metabolic activity, for example, so when they occur, cellular mechanisms are immediately activated to mitigate them. The same happens with the damage caused by exogenous agents, since the cell will do everything possible to diminish the adverse effects they can cause. The problem becomes apparent when the cell is unable to repair the damage or poorly repairs it, or repairs so much that the mechanisms are overwhelmed, when the damage remains in the DNA and a state of chromosomal instability is generated that can lead the cell to dysfunction and malignization. This state of chromosomal instability can be reflected in increased DNA breaks or micronuclei in exposed cells, which can be quantified by special methods such as the 'Comet Assay' and the 'Micronucleus Assay'. Since identifying DNA damage is a way of evaluating the toxic potential of the agents to which populations are exposed, it allows us to know their mechanisms of action and helps to understand the factors that influence the detriment in population's health.

Decrease of 5-hydroxymethylcytosine in primary cutaneous CD4+ small/medium sized pleomorphic T-cell lymphoproliferative disorder

Abstract Background: Primary cutaneous CD4+ small/medium-sized pleomorphic T-Cell lymphoproliferative disorder (PC-SMTLD) has been considered as a controversial dermatological disease that has been included in cutaneous T-cell lymphoma group, presenting most commonly as a solitary nodule and/or plaque with a specific and characteristic head and neck predilection. Due to the considerable overlap between PC-SMTLD and pseudolymphoma (PL), the differential diagnosis is often challenging. Methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, it has rarely been studied in cutaneous lymphomas. Objectives: The authors aimed to explore the role of differential 5-hmC immunostaining as a useful marker to distinguish PC-SMTLD from PL. Methods: Retrospective case series study with immunohistochemical and immunofluorescence analysis of 5-hmC was performed in PL and PC-SMTLD. Results: Significant decrease of 5-hmC nuclear staining was observed in PC-SMTLD when compared with PL (p<0.0001). By semi-quantitative grade integration, there were statistical differences in the final 5-hmC scores in the two study groups. The IF co-staining of 5-hmC with CD4 revealed a decrease of 5-hmC in CD4+ lymphocytes of PC-SMTLD. Study limitations: The small clinical sample size of the study. Conclusions: The immunorreactivity of 5-hmC in CD4+ lymphocytes was highly suggestive of a benign process as PL. Furthermore, the decrease of 5-hmC nuclear staining in PC-SMTLD indicated its lymphoproliferative status and helped to make the differential diagnosis with PL. © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

Research advance on the role of mitochondrial dysfunction and releasing mitochondrial DNA in sepsis-induced acute lung injury / 中华危重病急救医学

Sepsis-induced acute lung injury (ALI) is a serious condition with a high incidence. Mitochondrial dysfunction and the release of mitochondrial DNA (mtDNA) play a crucial role in the occurrence and development of sepsis-induced ALI. In sepsis, mitochondrial dysfunction causes energy depletion of cells and dysfunction of tissue cell repair mechanisms, leading to ALI. In addition, the release of mtDNA leads to a more intense inflammatory response, exacerbating sepsis-induced ALI. This article reviews the pathophysiological mechanism of mitochondrial dysfunction and mtDNA release in sepsis and the current research status, in order to provide direction for the evaluation, treatment and prevention of sepsis-induced ALI.

Study on OS-induced DNA damage from X-ray activation and cellular premature aging of HaCaT cells / 中国医学装备

Objective:To explore the changes of oxidative stress(OS),DNA damage and the occurrence of cellular premature aging of human immortalized keratinocytes(HaCaT)after that was radiated by X-ray with different doses.Methods:HaCaT cells were radiated by X-ray,and they were divided into 0 Gy group,5 Gy group and 10 Gy group according to the irradiation dose.The levels of intracellular reactive oxygen species(ROS)were detected by 2,7-Dichlorofluorescein diacetate(DCFH-DA)fluorescent probe,and the intracellular content of malondialdehyde(MDA)of lipid peroxidation products and the activity of superoxide dismutase(SOD)were measured by colorimetry.Immunofluorescence staining was used to detect the phosphorylated histone 2A variant(γ-H2AX)in HaCaT cells that were radiated by X-ray with different doses.Cell count kit-8(CCK-8)was used to detect the effect of X-ray with different doses on the proliferation of HaCaT cells after X-ray with different doses radiated them.β-Galactosidase staining was used to detect the proportion of premature aging cells.The changes of p21 and p53 protein expressions after X-ray irradiation were detected by Western blot.Results:After HaCaT cells were radiated by X-ray for 24h,the fluorescence intensity of 2',7'-Dichlorofluorescein(DCF)in 5 Gy and 10 Gy groups were significantly higher than that in the 0 Gy group,and the MDA contents of them were significantly higher than that in the control group,and the SOD activities of them were significantly lower than that in the control group(F=38.35,92.22,5.22,P<0.05),respectively.The change of γ-H2AX focus showed a dose-dependent significant increase at 1 h after irradiation,and the difference between them and control group was statistically significant(F=129.3,P<0.05).At 6h,24h and 48h after X-ray radiated HaCaT cells,the cell proliferation abilities of 5 Gy group and 10 Gy group were significantly decreased than that of 0 Gy group(F=116.41,62.20,34.29,P<0.01),and the β-Galactosidase activity of the two groups were significantly increased than that of 0 Gy group,and the difference was significant(F=1629.22,P<0.01).At 72h after X-ray with different doses radiated HaCaT cells,the expression levels of p21 and p53 proteins of 5 Gy group and 10 Gy group increased,and the differences of them among three groups were significant(F=104.4,66.69,P<0.01),respectively.Conclusion:Ionizing radiation can induce the occurrences of oxidative stress and DNA damage in HaCaT cells,and cause the occurrence of cellular premature aging.

Research progress in histone acetylation in radiation-related DNA damage / 中华放射肿瘤学杂志

Radiotherapy is a first-line treatment for a variety of malignant tumors by inducing DNA damage to kill tumor cells. However, tumor cells have different sensitivities to radiotherapy, ultimately leading to different therapeutic effects. Histone acetylation, regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC), is involved in the regulation of cell radiation sensitivity by influencing DNA damage repair. The main mechanisms are recruiting DNA repair related proteins and mediating chromatin dynamic changes. In this article, the role of histone acetylation modification in tumor radiotherapy was reviewed, aming to provide the basis for the radiotherapy sensitization strategy based on histone acetylation.

Diagnostic value of HPV-DNA typing combined with serum NLR and DCLK1 for cervical cancer / 中国现代医生

@#Objective To investigate the value of receiver operating curve human papilloma virus(HPV)-DNA typing combined with serum neutrophil lymphocyte ratio(NLR)and bicorticoid kinase 1(DCLK1)levels in the early diagnosis of cervical cancer.Methods A total of 120 patients with early cervical cancer diagnosed in our obstetrics and gynecology department from August 2018 to June 2022 were randomly included as cervical cancer group,and 120 patients with benign lesions were included as benign group.The level of DCLK1 was detected by ELISA;NLR was detected by automatic blood cell analyzer;HPV subtypes in cervical secretions were detected by HPV genotyping gene chip detection system;the cut-off values of serum NLR and DCLK1 levels in the diagnosis of cervical cancer were analyzed by using the receiver operator curve(ROC);four table method was applied to analyze the diagnostic value of HPV-DNA typing,serum NLR,DCLK1 levels alone and in combination for cervical cancer.Results Compared with benign group,the levels of serum NLR and DCLK1 in cervical cancer group were obviously higher(P<0.05).The positive rate of HR-HPV in cervical cancer group was obviously higher than that in benign group(P<0.05).The ROC curve was drawn with serum NLR and DCLK1 levels as test variables,the results showed that the AUC of serum NLR and DCLK1 predicting early cervical cancer was 0.724 and 0.718,respectively,and the cut-off value was 3.08 and 3.32,respectively.HPV-DNA typing combined with serum NLR and DCLK1 detected 18 false positives and 17 false negatives,Kappa value was 0.725,which was consistent with pathological results.The sensitivity,negative predictive value and accuracy of HPV-DNA typing combined with serum NLR and DCLK1 levels in the diagnosis of early cervical cancer were obviously higher than those of HPV-DNA typing,serum NLR and DCLK1 levels alone(P<0.05).Conclusion The results of HPV-DNA typing combined with NLR and DCLK1 in the diagnosis of early cervical cancer are highly consistent with the pathological results,and the sensitivity and accuracy are obviously improved.

Value of HPV DNA,HPV E6/E7 protein and TCT in cervical intraepithelial neoplasia and cervical cancer screening / 中国现代医生

@#Objective To investigate the value of human papilloma virus(HPV)DNA,HPV E6/E7 protein and thin-prep cytology test(TCT)in cervical intraepithelial neoplasia(CIN)and cervical cancer screening.Methods A total of 190 adult women who received early cervical cancer screening in Department of Gynecology,Zhuji People's Hospital from July 2021 to June 2022 were selected as the study objects.HPV DNA,HPV E6/E7 protein and TCT were detected,respectively,and further colposcopic biopsy was performed.The diagnostic efficacy of HPV DNA,HPV E6/E7 protein and TCT in patients with different lesions were compared.Results The positive rates of HPV DNA,HPV E6/E7 protein,TCT and combined detection in CIN3 and cervical cancer patients were significantly higher than those in cervicitis patients(P<0.05).The positive rates of HPV DNA,HPV E6/E7 protein,TCT and combined detection in cervical cancer patients were significantly higher than those in CIN1 patients(P<0.05).The positive rates of HPV DNA,HPV E6/E7 protein,TCT and combined detection in CIN2+ patients were significantly higher than those in CIN1-patients.The sensitivity,specificity,positive predictive value and negative predictive value of HPV DNA,HPV E6/E7 protein and TCT in the diagnosis of high-grade lesions were 90.80%,30.10%,52.32%and 79.48%,respectively.Conclusion HPV DNA,HPV E6/E7 protein and TCT can be used as screening methods for cervical cancer and precancerous lesions,with the combination of the three being the most sensitive.

Effects of perinatal exposure to benzo[a]pyrene on the expressionof PDX-1 and TFAM in pancreas and mitochondrial DNA copynumber in offspring rats / 预防医学

Objective@#To observe the effects of perinatal exposure to benzo[a]pyrene (B[a]P) on the expression of pancreatic duodenal homeobox-1 (PDX-1) and mitochondrial transcription factor A (TFAM) and mitochondrial DNA copy number in offspring mice, and to explore the role of maternal exposure to B[a]P in the pancreatic function damage of offspring mice.@*Methods@#Forty pregnant rats were randomly divided into the control group, the lowest dose group (2 μg/kg), the low dose group (200 μg/kg), medium dose group (800 μg/kg) and high dose group (1 600 μg/kg), with 8 rats in each group. From day 1 of pregnancy, each exposed group was given 0.2 mL/100 g body weight of B[a]P and corn oil mixture by gavage once a day until 3 weeks after delivery, while the control group was given the same dose of corn oil. The pancreatic tissue of three-week-old mice were collected after abdominal anesthesia for insulin immunohistochemical detection. The protein and mRNA expression levels of PDX-1 and TFAM, as well as mitochondrial DNA copy number were detected. Spearman rank correlation analysis was used to analyze the correlation between B[a]P exposure dose and the above indicators.@*Results@#The insulin-positive area ratio and average optical density of insulin in the medium and the high dose groups were significantly lower than those in the control group (all P<0.05). The insulin-positive area ratio and average optical density of insulin were negatively correlated with the B[a]P dose (rs=-0.862 and -0.858, both P<0.05). The protein expression levels of PDX-1 and TFAM in the high dose group were significantly lower than those in the control group (both P<0.05). The protein expression levels of PDX-1 and TFAM were negatively correlated with the B[a]P dose (rs=-0.756 and -0.799, both P<0.05). The mRNA expression levels of PDX-1 and mitochondrial DNA copy number in the medium and high dose groups were significantly lower than those in the control group, and the mRNA expression level of TFAM in the high dose group was significantly lower than that in the control group (all P<0.05). The mRNA expression levels of PDX-1, TFAM, and mitochondrial DNA copy number were negatively correlated with the B[a]P dose (rs=-0.722, -0.550 and -0.840, all P<0.05).@*Conclusion@#Perinatal exposure to B[a]P can induce the damage of islet β cells in offspring rats, which may be related to the decreased expression of PDX-1 and TFAM and the copy number of mitochondrial DNA.

Ribosomal DNA copy number variation in peripheral blood and its influencing factors among patients with pneumoconiosis / 预防医学

Objective@#To explore the changes in ribosomal DNA copy number in peripheral blood among patients with pneumoconiosis and its influencing factors, so as to provide insights into prevention and treatment of pneumoconiosis.@*Methods@#Eighty-eight patients with pneumoconiosis who visited a designated hospital and 71 community residents with no history of pneumoconiosis or dust exposure were selected as the pneumoconiosis group and control group, and age, smoking history, drinking history and cumulative years of exposure to dust were collected through questionnaire surveys. The copy number of 45S rDNA and 5S rDNA was detected using real-time fluorescence quantitative PCR, and the differences between the two groups were compared. Factors affecting the copy number of 45S rDNA and 5S rDNA were identified by a multiple linear regression model.@*Results@#The pneumoconiosis group had a median age of 56.00 (interquartile range, 15.25) and a mean cumulative dust exposure duration of (12.40±8.08) years, with 56.82% smoking and 62.50% drinking. The control group had a median age of 64.00 (interquartile range, 37.00) years, with 32.39% smoking and 26.76% drinking. The median copy number of 45S rDNA in the pneumoconiosis group was 1.29 (interquartile range, 0.59), which was lower than 2.10 (interquartile range, 1.88) in the control group; the median copy number of 5S rDNA in the pneumoconiosis group was 5.33 (interquartile range, 0.85), which was higher than 4.66 (1.34) in the control group (both P<0.05). Multiple linear regression analysis identified age (β=-0.034) and pneumoconiosis (β=-1.595) as factors affecting 45S rDNA copy number, age (β=-0.013) as a factor affecting 5S rDNA copy number, and age (β=0.018) as a factor affecting 5S rDNA copy number in the pneumoconiosis group (all P<0.05).@*Conclusions@#Compared with community residents with no history of pneumoconiosis or dust exposure, the copy number of 45S rDNA in peripheral blood among patients with pneumoconiosis is reduced and the copy number of 5S rDNA is increased.

Interactions of multi-target stool DNA, intestinal flora, carcinoembryonic antigen and fruit intake on the risk of colorectal cancer / 预防医学

Objective@#To explore the interaction of multi-target stool DNA (MT-sDNA), intestinal flora and environmental factors in the development of colorectal cancer, so as to provide insights into pathogenesis study of colorectal cancer.@*Methods@#A total of 54 cases of colorectal cancer from the First Affiliated Hospital of Ningbo University were included in the case group and 51 healthy subjects were included in the control group. Demographic information, diet and family history of colorectal cancer were collected by a questionnaire survey. MT-sDNA, intestinal flora, cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and other tumor markers were detected. Interactions of MT-sDNA, intestinal flora and environmental factors with the development of colorectal cancer was analyzed by multifactor dimensionality reduction (MDR), crossover analysis and additive model.@*Results@#The case group included 20 males (37.04%) and 34 females (62.96%), and had a mean age of (64.89±9.72) years. The control group included 24 males (47.06%) and 27 females (52.94%), and had a mean age of (53.94±10.33) years. MDR analysis showed that subjects with both high absolute intestinal flora indexes and positive MT-sDNA had an increased risk of colorectal cancer (OR=3.782, 95%CI: 1.190-5.034). Crossover analysis showed that subjects with positive MT-sDNA and >5 μg/L of CEA had an increased risk of colorectal cancer (OR=2.121, 95%CI: 1.162-4.033). Additive model analysis showed that MT-sDNA had positive additive interaction with CEA (SI=3.687, 95%CI: 1.229-7.238), and MT-sDNA had negative additive interaction with fruit intake (SI=0.145, 95%CI: 0.020-0.753).@*Conclusion@#Positive MT-sDNA can synergistically increase the risk of colorectal cancer with high intestinal flora index and CEA, and fruit intake can reduce the risk of colorectal cancer in MT-sDNA-positive population.