MicroRNA biomarkers in leprosy: insights from the Northern Brazilian Amazon population and their implications in disease immune-physiopathology

Leprosy, or Hansen’s Disease, is a chronic infectious disease caused by Mycobacterium leprae that affects millions of people worldwide. Despite persistent efforts to combat it leprosy remains a significant public health concern particularly in developing countries. The underlying pathophysiology of the disease is not yet fully understood hindering the development of effective treatment strategies. However, recent studies have shed light on the potential role of microRNAs (miRNAs), small non-coding RNA molecules that can regulate gene expression, as promising biomarkers in various disease, including leprosy. This study aimed to validate a set of nine circulating miRNAs to propose new biomarkers for early diagnosis of the disease. Hsa-miR-16-5p, hsa-miR-106b-5p, hsa-miR-1291, hsa-miR-144-5p, and hsa-miR-20a-5p showed significant differential expression between non-leprosy group (non-LP) and leprosy group (LP), accurately discriminating between them (AUC > 0.75). In addition, our study revealed gender-based differences in miRNA expression in LP. Notably, hsa-miR-1291 showed higher expression in male LP, suggesting its potential as a male-specific biomarker. Similarly, hsa-miR-16-5p and hsa-miR-20a-5p displayed elevated expression in female LP, indicating their potential as female-specific biomarkers. Additionally, several studied miRNAs are involved in the dysregulation of apoptosis, autophagy, mitophagy, cell cycle, and immune system in leprosy. In conclusion, the validation of miRNA expression highlights several miRNAs as potential biomarkers for early diagnosis and provides new insights into the pathogenesis of the disease

ncRNAs: an unexplored cellular defense mechanism in leprosy

Leprosy is an infectious disease primarily caused by the obligate intracellular parasite Mycobacterium leprae. Although it has been considered eradicated in many countries, leprosy continues to be a health issue in developing nations. Besides the social stigma associated with it, individuals affected by leprosy may experience nerve damage leading to physical disabilities if the disease is not properly treated or early diagnosed. Leprosy is recognized as a complex disease wherein socioenvironmental factors, immune response, and host genetics interact to contribute to its development. Recently, a new field of study called epigenetics has emerged, revealing that the immune response and other mechanisms related to infectious diseases can be influenced by noncoding RNAs. This review aims to summarize the significant advancements concerning non-coding RNAs in leprosy, discussing the key perspectives on this novel approach to comprehending the pathophysiology of the disease and identifying molecular markers. In our view, investigations on non-coding RNAs in leprosy hold promise and warrant increased attention from researches in this field

Roles and Mechanisms of the Long Noncoding RNAs in Cervical Cancer

Cervical cancer (CC) continues to be one of the leading causes of death for women across the world. Although it has been determined that papillomavirus infection is one of the main causes of the etiology of the disease, genetic and epigenetic factors are also required for its progression. Among the epigenetic factors are included the long noncoding RNAs (lncRNAs), transcripts of more than 200 nucleotides (nt) that generally do not code for proteins and have been associated with diverse functions such as the regulation of transcription, translation, RNA metabolism, as well as stem cell maintenance and differentiation, cell autophagy and apoptosis. Recently, studies have begun to characterize the aberrant regulation of lncRNAs in CC cells and tissues, including Homeobox transcript antisense RNA (HOTAIR), H19, Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), Cervical Carcinoma High-Expressed 1 (CCHE1), Antisense noncoding RNA in the inhibitors of cyclin-dependent kinase 4 (ANRIL), Growth arrest special 5 (GAS5) and Plasmacytoma variant translocation 1 (PVT1). They have been associated with several disease-related processes such as cell growth, cell proliferation, cell survival, metastasis and invasion as well as therapeutic resistance, and are novel potential biomarkers for diagnosis and prognosis in CC. In this review, we summarize the current literature regarding the knowledge we have about the roles and mechanisms of the lncRNAs in cervical neoplasia

Evaluación de polimorfismos de los genes Timidilato sintasa, Metilentetrahidrofolato reductasa y Metionina sintasa en tumores de mama

Breast cancer (BC) is the most common cancer among women in the world and Brazil, after nonmelanoma skin cancer. Polymorphisms in genes involved in the folate pathway have been associated as possible etiological factors of this disease. Thymidylate synthase (TYMS) codes for the thymidylate synthase, responsible for the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). TYMS has a polymorphic tandem repeat in the 5'-UTR region (TSER), which generally contains a triple (3R) or double (2R) repeat of a 28 bp sequence. It is thought that the TSER variants are functionally relevant and are associated with BC risk. Another polymorphism in TYMS is 1494del6 and consists of the variation of a 6 bp sequence (TTAAAG) at position 1494 of the 3'-UTR region. These allelic variants are closely related to the level of expression of the enzyme. Methylenetetrahydrofolate reductase codes for the 5,10- methylenetetrahydrofolate reductase, which regulates the balance between cell methylation and nucleic acid synthesis, providing methyl groups for the conversion of homocysteine to methionine. Within the polymorphisms of MTHFR, the SNPs C677T and A1298C generate a reduced enzymatic activity, affecting the synthesis of nucleic acids and the availability of methyl groups for biochemical processes, which could increase BC risk. Methionine synthase (MTR) codes for the methionine synthase, which catalyzes the remethylation of homocysteine to methionine, an essential amino acid and precursor of S-adenosylmethionine, which is a universal donor of methyl groups involved in methylation reactions, including DNA methylation. The role of this polymorphism in cancer risk is still controversial. The aim of this study was to determine if the polymorphisms of the TYMS, MTHFR and MTR genes increase the BC risk. We worked with 61 samples of patients and 35 controls, it was carried out DNA extraction and purification, PCR amplification of DNA fragments including polymorphisms and their subsequent analysis directly through gel visualization, by PCR-RFLP and/or by automatic sequencing. Genotypic and allelic frequencies were determined and were related to the clinical characteristics of the patients and the molecular type of tumor. An analysis of statistical significance was carried out to evaluate the associations of all the polymorphisms with the risk of developing BC and the clinical characteristics of the patients. It was found that 3R allele of TSER and T and C alleles of C677T and A1298C could be associated to BC, although without statistical significance, and TSER and 1494del6 polymorphisms of TYMS could be related to the risk of developing more aggressive breast tumors, although the association is not statistically significant.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoO câncer de mama (CM) é tipo de câncer mais comum entre as mulheres no mundo e no Brasil, depois do câncer de pele não melanoma. Polimorfismos genéticos em genes da via do folato têm sido associados como fatores na etiologia desta doença. Timidilato sintase (TYMS) codifica a timidilato sintase, responsável pela conversão de desoxiuridina monofosfato (dUMP) em desoxitimidina monofosfato (dTMP). TYMS tem uma repetição em tandem polimórfica na região 5’-UTR (TSER) que contém, geralmente, uma tripla (3R) ou dupla (2R) repetição de uma sequência de 28 pb. Acredita-se que as variantes do TSER sejam funcionalmente relevantes e estejam hipoteticamente associadas ao risco de CM. Outro polimorfismo em TYMS é 1494del6, uma variação de uma sequência de 6 pb (TTAAAG) na posição 1494 da região 3'-UTR. Estas variantes alélicas estão intimamente relacionadas com o nível de expressão da enzima. Metilenotetrahidrofolato redutase codifica a 5,10-metileno-tetrahidrofolato redutase que regula o equilíbrio entre a metilação celular e a síntese de ácidos nucléicos, fornecendo grupos metil para a conversão de homocisteína em metionina. Entre os polimorfismos de MTHFR estão os SNPs C677T e A1298C que geram uma atividade enzimática reduzida que afeta a síntese dos ácidos nucleicos e a disponibilidade de grupos metil para processos bioquímicos, que podem aumentar o risco de CM. Metionina sintase codifica a metionina sintase, que catalisa a remetilação de homocisteína a metionina, um aminoácido precursor essencial da S-adenosilmetionina, que é um doador de metilo universal envolvido em reações de metilação, incluindo a metilação de DNA. O papel desse polimorfismo no risco de câncer ainda é controverso. O objetivo deste estudo foi determinar se os polimorfismos dos genes TYMS, MTHFR e MTR aumentam o risco de desenvolver CM. Para isso, foram utilizadas 61 amostras de pacientes e 35 de controles para as quais foi realizada a extração e purificação do DNA, a amplificação por PCR dos fragmentos contendo os polimorfismos e sua posterior análise diretamente através da visualização em gel, por PCR-RFLP e/ou por sequenciamento automático. Realizou-se uma análise de significância estatística para avaliar as associações de todos os polimorfismos estudados com o risco de desenvolver CM e as características clínicas das pacientes. Verificou-se que o alelo 3R de TSER e os alelos T e C de C677T e A1298C poderiam estar associados ao CM, mas sem significância estatística, e que os polimorfismos TSER e 1494del6 do TYMS poderiam estar relacionados ao risco de desenvolver tumores de mama mais agressivos, embora a associação não seja estatisticamente significante

La expresión corporal en educación física : propuesta curricular desde la administración educativa

Resumen basado en el de la publicaciónSe analiza la expresión corporal en la Educación Física y se presenta un estudio de caso de un Match de improvisación. La expresión corporal es el instrumento con el cual se producen las variadas formas del arte del movimiento. Es fundamental en el proceso de comunicación y éste debe ser interactivo y dinámico. Se analiza la expresión corporal como medio educativo para la formación integral del alumnado. En el estudio del caso, se muestra cómo se aplica al marco escolar y en qué puede ayudar.AndalucíaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

La orientación deportiva en el marco escolar : propuesta educativa para la educación física en secundaria

Resumen basado en el de la publicaciónSe ofrecen directrices de cómo llevar a cabo trabajos de orientación deportivo en los centros de Educación Secundaria y se contextualiza dentro del marco escolar y su currículum. La orientación es un deporte consistente en una carrera individual cronometrada donde los participantes usan un mapa esencial y una brújula para recorrer en el orden adecuado diferentes puntos de control. Se explican las diversas modalidades de orientación existentes: como actividad en la naturaleza, como deporte competitivo, como actividad de ocio al aire libre y como modo de mantenerse en forma. La orientación guarda relación con el currículo oficial de Educación Física y forma parte del bloque de contenidos de Actividades en el Medio Natural.AndalucíaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

La expresión corporal en educación física : propuesta curricular desde la administración educativa

Resumen basado en el de la publicaciónSe analiza la expresión corporal en la Educación Física y se presenta un estudio de caso de un Match de improvisación. La expresión corporal es el instrumento con el cual se producen las variadas formas del arte del movimiento. Es fundamental en el proceso de comunicación y éste debe ser interactivo y dinámico. Se analiza la expresión corporal como medio educativo para la formación integral del alumnado. En el estudio del caso, se muestra cómo se aplica al marco escolar y en qué puede ayudar.AndalucíaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Las actividades extraescolares y complementarias en el marco escolar : posibilidades educativas desde la educación física en secundaria

La oferta de actividades extraescolares deportivas es un elemento social de primer orden que deben estar reguladas por los proyectos de centro, como elemento del papel educativo de los mismos. Se analiza el concepto de actividad extraescolar, la normativa que las regula, el papel del Ampa y criterios para su organización. Se centra en las actividades desde la educación física y en las complementarias en el entorno natural.AndalucíaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

La educación para la paz : propuestas educativas desde la educación física escolar

Resumen basado en el de la publicaciónSe presenta una iniciativa en la que se trata de incluir un contenido educativo sobre la paz y valores necesarios para la integración del alumno mediante la Educación Física. Para poder educar a los alumnos mediante la paz, es necesario poner en marcha un plan de convivencia en el centro capaz de inculcar valores éticos y cívicos. La Educación Física se muestra como una de las materias con multitud de actividades orientadas a su consecución. Practicando juegos y deportes se debe hacer hincapié en la utilización del diálogo para la resolución de conflictos, desarrollando así actitudes de compañerismo ante los demás.AndalucíaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]