Epithelial Dual Oxidase 2 Shapes the Mucosal Microbiome and Contributes to Inflammatory Susceptibility.

Reactive oxygen species (ROS) are highly reactive molecules formed from diatomic oxygen. They act as cellular signals, exert antibiotic activity towards invading microorganisms, but can also damage host cells. Dual oxidase 2 (DUOX2) is the main ROS-producing enzyme in the intestine, regulated by cues of the commensal microbiota and functions in pathogen defense. DUOX2 plays multiple roles in different organs and cell types, complicating the functional analysis using systemic deletion models. Here, we interrogate the precise role of epithelial DUOX2 for intestinal homeostasis and host-microbiome interactions. Conditional Duox2∆IEC mice lacking DUOX2, specifically in intestinal epithelial cells, were generated, and their intestinal mucosal immune phenotype and microbiome were analyzed. Inflammatory susceptibility was evaluated by challenging Duox2∆IEC mice in the dextran sodium sulfate (DSS) colitis model. DUOX2-microbiome interactions in humans were investigated by paired analyses of mucosal DUOX2 expression and fecal microbiome data in patients with intestinal inflammation. Under unchallenged conditions, we did not observe any obvious phenotype of Duox2∆IEC mice, although intestinal epithelial ROS production was drastically decreased, and the mucosal microbiome composition was altered. When challenged with DSS, Duox2∆IEC mice were protected from colitis, possibly by inhibiting ROS-mediated damage and fostering epithelial regenerative responses. Finally, in patients with intestinal inflammation, DUOX2 expression was increased in inflamed tissue, and high DUOX2 levels were linked to a dysbiotic microbiome. Our findings demonstrate that bidirectional DUOX2-microbiome interactions contribute to mucosal homeostasis, and their dysregulation may drive disease development, thus highlighting this axis as a therapeutic target to treat intestinal inflammation.

Mitochondrial Function and Microbial Metabolites as Central Regulators of Intestinal Immune Responses and Cancer.

Energy and anabolic metabolism are essential for normal cellular homeostasis but also play an important role in regulating immune responses and cancer development as active immune and cancer cells show an altered metabolic profile. Mitochondria take a prominent position in these metabolic reactions. First, most key energetic reactions take place within or in conjunction with mitochondria. Second, mitochondria react to internal cues from within the cell but also to external cues originating from the microbiota, a vast diversity of associated microorganisms. The impact of the microbiota on host physiology has been largely investigated in the last decade revealing that the microbiota contributes to the extraction of calories from the diet, energy metabolism, maturation of the immune system and cellular differentiation. Thus, changes in the microbiota termed dysbiosis have been associated with disease development including metabolic diseases, inflammation and cancer. Targeting the microbiota to modulate interactions with the mitochondria and cellular metabolism to delay or inhibit disease development and pathogenesis appears an attractive therapeutic approach. Here, we summarize recent advances in developing the therapeutic potential of microbiota-mitochondria interactions for inflammation and cancer.

The Interaction of Human Pathogenic Fungi With C-Type Lectin Receptors.

Fungi, usually present as commensals, are a major cause of opportunistic infections in immunocompromised patients. Such infections, if not diagnosed or treated properly, can prove fatal. However, in most cases healthy individuals are able to avert the fungal attacks by mounting proper antifungal immune responses. Among the pattern recognition receptors (PRRs), C-type lectin receptors (CLRs) are the major players in antifungal immunity. CLRs can recognize carbohydrate ligands, such as ß-glucans and mannans, which are mainly found on fungal cell surfaces. They induce proinflammatory immune reactions, including phagocytosis, oxidative burst, cytokine, and chemokine production from innate effector cells, as well as activation of adaptive immunity via Th17 responses. CLRs such as Dectin-1, Dectin-2, Mincle, mannose receptor (MR), and DC-SIGN can recognize many disease-causing fungi and also collaborate with each other as well as other PRRs in mounting a fungi-specific immune response. Mutations in these receptors affect the host response and have been linked to a higher risk in contracting fungal infections. This review focuses on how CLRs on various immune cells orchestrate the antifungal response and on the contribution of single nucleotide polymorphisms in these receptors toward the risk of developing such infections.

[Advances in dengue virus research in Colombia: the role of cellular microRNAs as an anti-dengue virus response]. / Avances en la investigación del virus dengue en Colombia: papel de los microARNs celulares en la respuesta anti-dengue virus.

Dengue is one of the most important mosquito-borne diseases, and its incidence has increased at an alarming rate in recent years, becoming a real public health problem. Currently, there is no vaccine or medication or proper treatment for dengue control. Considering this situation, it is necessary to prioritize the search for new alternatives and strategies for dengue prevention and control, in order to reduce not only the economic burden of endemic countries, but also to improve the quality of life of patients. In this regard, a brief reflection on some aspects related to the search for new alternatives in Colombia is presented. This is focused on the use of microRNAs, which could be a new strategy with great therapeutic potential.

Avances en la investigación del virus dengue en Colombia: papel de los microARNs celulares en la respuesta anti-dengue virus / Advances in dengue virus research in Colombia: the role of cellular microRNAs as an anti-dengue virus response

Dengue is one of the most important mosquito-borne diseases, and its incidence has increased at an alarming rate in recent years, becoming a real public health problem. Currently, there is no vaccine or medication or proper treatment for dengue control. Considering this situation, it is necessary to prioritize the search for new alternatives and strategies for dengue prevention and control, in order to reduce not only the economic burden of endemic countries, but also to improve the quality of life of patients. In this regard, a brief reflection on some aspects related to the search for new alternatives in Colombia is presented. This is focused on the use of microRNAs, which could be a new strategy with great therapeutic potential.

El dengue es una de las enfermedades más importantes transmitidas por mosquitos y su incidencia ha aumentado a un ritmo alarmante en los últimos años, al punto que se ha convertido en un verdadero problema de salud pública. Actualmente no existe ni vacuna, ni un medicamento o tratamiento adecuado para el control del dengue. Con dichos antecedentes, es necesario priorizar en la búsqueda de nuevas alternativas o estrategias de control y prevención del dengue con miras a disminuir no sólo la carga económica de los países endémicos, sino también a mejorar la calidad de vida de los pacientes. En este sentido, se presenta una breve reflexión sobre algunos aspectos relacionados con la búsqueda de nuevas alternativas en Colombia, enfocadas en el uso de los microARNs, que podrían constituir una nueva estrategia con un gran potencial terapéutico, dado que tendrían el potencial de contrarrestar algunas infecciones virales crónicas.

Overexpression of miR-484 and miR-744 in Vero cells alters Dengue virus replication

BACKGROUND Dengue is considered one of the world’s most important mosquito-borne diseases. MicroRNAs (miRNAs) are small non-coding single-stranded RNAs that play an important role in the regulation of gene expression in eukaryotes. Although miRNAs possess antiviral activity against many mammalian-infecting viruses, their involvement in Dengue virus (DENV) replication remains poorly understood. OBJECTIVE To determine the role of miR-484 and miR-744 in DENV infection and to examine whether DENV infection alters the expression of both miRNAs. METHODS We used bioinformatics tools to explore the relationship between DENV and cellular miRNAs. We then overexpressed miR-484 or miR-744 in Vero cells to examine their role in DENV replication using flow cytometry, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), and western blotting. FINDINGS We found several cellular miRNAs that target a conserved region within the 3′ untranslated region (3′ UTR) of the genome of the four DENV serotypes and found that overexpression of miR-484 or miR-744 inhibits infection by DENV-1 to DENV-4. Furthermore, we observed that DENV RNA might be involved in the downregulation of endogenous miR-484 and miR-744. CONCLUSION Our study identifies miR-484 and miR-744 as two possible restriction host factors against DENV infection. However, further studies are needed to directly verify whether miR-484 and miR-744 both have an anti-DENV effect in vivo.

Overexpression of miR-484 and miR-744 in Vero cells alters Dengue virus replication.

BACKGROUND: Dengue is considered one of the world's most important mosquito-borne diseases. MicroRNAs (miRNAs) are small non-coding single-stranded RNAs that play an important role in the regulation of gene expression in eukaryotes. Although miRNAs possess antiviral activity against many mammalian-infecting viruses, their involvement in Dengue virus (DENV) replication remains poorly understood. OBJECTIVE: To determine the role of miR-484 and miR-744 in DENV infection and to examine whether DENV infection alters the expression of both miRNAs. METHODS: We used bioinformatics tools to explore the relationship between DENV and cellular miRNAs. We then overexpressed miR-484 or miR-744 in Vero cells to examine their role in DENV replication using flow cytometry, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), and western blotting. FINDINGS: We found several cellular miRNAs that target a conserved region within the 3' untranslated region (3' UTR) of the genome of the four DENV serotypes and found that overexpression of miR-484 or miR-744 inhibits infection by DENV-1 to DENV-4. Furthermore, we observed that DENV RNA might be involved in the downregulation of endogenous miR-484 and miR-744. CONCLUSION: Our study identifies miR-484 and miR-744 as two possible restriction host factors against DENV infection. However, further studies are needed to directly verify whether miR-484 and miR-744 both have an anti-DENV effect in vivo.

Arquetipos, terminologías e interoperabilidad semántica en salud / Archetypes, terminologies and semantic interoperability in health

La falta de aplicación de estándares repercute en lo negativo en la calidad de la prestación de servicios de salud, lo cual se ve reflejado en un alto porcentaje de errores médicos prevenibles, que son causados por la falta de acceso inmediato a la información de salud. Es por esto que en la actualidad, existe una necesidad hacia sistemas distribuidos e interconectados, que favorezcan la representación y comunicación de los sistemas de historia clínica electrónica, de tal forma que permitan la interoperabilidad. Es aquí donde la arquitectura de modelo dual surge como una solución a los problemas clásicos de evolución y mantenimiento de los sistemas de información y por consiguiente, como la piedra angular para alcanzar la llamada interoperabilidad semántica. La interoperabilidad es la clave para la atención efectiva en el ámbito de la salud ya que aumenta la calidad de la atención, reduce los costos, y mejora los servicios, lo que se traduce en una atención más segura y eficiente. En la presente revisión, se pretende como objetivo, describir los elementos más importantes a la hora de expresar la información clínica, como son las terminologías para codificar la información, un modelo de referencia para expresar las características generales de los componentes de un registro clínico, y de unos arquetipos que definen los conceptos clínicos presentes; todos estos como componentes indispensables para alcanzar dicha interoperabilidad.

The lack of application of standards has a negative effect on the quality of health service provision which is shown in the high percentage of preventable medical errors that are caused by lack of immediate access to health information. That is the reason why it is necessary today to move towards distributed and interconnected systems favoring representation and communication of electronic health record systems so that they allow interoperability. This is the moment when the dual model architecture emerges as a solution to the clasic problems of evolution and maintenance of the information systems and consequently, as a milestone to reach the so called semantic interoperability. Interoperability is the key to effective care in health since it increases the quality of care, reduces costs and improves services. All the above-mentioned brings more efficient and safer care. The present literature review was aimed at describing the most important elements to express clinical information such as terminologies to coding information, a reference model to express the general characteristics of the clinical register components and those of archetypes that define the present clinical concepts. All of them are indispensable elements to reach interoperability.

Terminologies and classification systems in biomedical sciences

Standards terminologies emerged as an attempt to reduce the diversity terminology in scientific languages, facilitating good communication, which is the basis of all scientific research. This review explains principles and applications associated with terminologies and classification systems focusing mainly on the field of biomedical sciences. The research was conducted on scientific databases, books and network using the keywords: Terminologies, Classification systems, Medical Informatics, Electronic Health Records systems, Interoperability, Ontologies and Bio-ontologies. This review is intended to explain that terminologies facilitate good communication, reducing terminology diversity and they are not static systems. They can "evolve" to more complex structures like biomedical ontologies, with the aim of being used with multiple purposes beginning with the efficient transfer of information, to the processing of information as a result of biological research for its understanding(AU)

Las terminologías surgieron como un intento de reducir la diversidad terminológica en el lenguaje científico, facilitando una buena comunicación, que es la base de toda investigación científica. Esta revisión explica los principios y las aplicaciones asociadas con las terminologías y los sistemas de clasificación, centrándose en el campo de las ciencias biomédicas. La investigación fue realizada en bases de datos científicas, libros e internet, utilizando las palabras clave: Terminología, sistemas de clasificación, interoperabilidad, ontologías y Bio-ontologías. Esta revisión tiene por objeto explicar que las terminologías facilitan una buena comunicación, reduciendo la diversidad terminológica y además explicando que no son sistemas estáticos. Ellas pueden evolucionar para formar estructuras complejas como ontologías biomédicas, con el objetivo de ser utilizadas con múltiples propósitos que comienzan con la transferencia eficiente de la información, hasta el procesamiento de información obtenida de la investigación biológica para su comprensión(AU)