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.

Whole mitogenome sequencing uncovers a relation between mitochondrial heteroplasmy and leprosy severity.

BACKGROUND: In recent years, the mitochondria/immune system interaction has been proposed, so that variants of mitochondrial genome and levels of heteroplasmy might deregulate important metabolic processes in fighting infections, such as leprosy. METHODS: We sequenced the whole mitochondrial genome to investigate variants and heteroplasmy levels, considering patients with different clinical forms of leprosy and household contacts. After sequencing, a specific pipeline was used for preparation and bioinformatics analysis to select heteroplasmic variants. RESULTS: We found 116 variants in at least two of the subtypes of the case group (Borderline Tuberculoid, Borderline Lepromatous, Lepromatous), suggesting a possible clinical significance to these variants. Notably, 15 variants were exclusively found in these three clinical forms, of which five variants stand out for being missense (m.3791T > C in MT-ND1, m.5317C > A in MT-ND2, m.8545G > A in MT-ATP8, m.9044T > C in MT-ATP6 and m.15837T > C in MT-CYB). In addition, we found 26 variants shared only by leprosy poles, of which two are characterized as missense (m.4248T > C in MT-ND1 and m.8027G > A in MT-CO2). CONCLUSION: We found a significant number of variants and heteroplasmy levels in the leprosy patients from our cohort, as well as six genes that may influence leprosy susceptibility, suggesting for the first time that the mitogenome might be involved with the leprosy process, distinction of clinical forms and severity. Thus, future studies are needed to help understand the genetic consequences of these variants.

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.

[Epidemiological behavior of leprosy in several Latin American countries, 2011-2020Comportamento epidemiológico da hanseníase em vários países da América Latina, 2011-2020]. / Comportamiento epidemiológico de la lepra en varios países de América Latina, 2011-2020.

Objective: To describe the epidemiological behavior of leprosy in several Latin American countries during 2011-2020, based on World Health Organization (WHO) indicators. Methods: Cross-sectional, descriptive and quantitative study with official data on incidence and prevalence in the general population, children, clinical form and cases with grade 2 disability from WHO records between 2011 and 2020. The eight countries in Latin America that reported most cases were selected and analyses were carried out using simple descriptive and comparative statistics between different variables. Results: During the study period, 301 312 cases of leprosy were reported in the selected countries: Argentina, Brazil, Colombia, Cuba, Dominican Republic, Mexico, Paraguay, and Venezuela. Brazil is the only country in the region with a prevalence greater than 1 per 10 000, representing 93.77% of all cases. Brazil and the Dominican Republic showed an increase in prevalence during 2011-2019, while in other countries the trend was decreasing. The disease is more frequent in men, and multibacillary cases significantly exceed paucibacillary ones. Brazil showed the highest incidences of cases of childhood leprosy and grade 2 disability during the evaluated period. Conclusion: In Latin America, leprosy is only considered a public health problem in Brazil; however, most countries in the region continue to report cases annually, revealing a lack of adequate medical care. This study confirmed the importance of active surveillance, early diagnosis and planning of actions against the disease in all the countries evaluated with the aim of reducing its transmission.

Objetivo: Descrever o comportamento epidemiológico da hanseníase em vários países de América Latina durante 2011-2020, tomando como base os indicadores da Organização Mundial da Saúde (OMS). Método: Estudo transversal, descritivo e quantitativo com dados oficiais de incidência e prevalência na população geral, em crianças, forma clínica e casos com incapacidade de grau 2 nos registros da OMS entre 2011 e 2020. Se selecionaram os oito países da América Latina que relataram a maioria dos casos e as análises foram avaliadas por meio de estatísticas descritivas e comparativas simples entre as variáveis. Resultados: No período, foram notificados 301 312 casos de hanseníase nos países selecionados: Argentina, Brasil, Colômbia, Cuba, México, Paraguai, República Dominicana e Venezuela. O Brasil é o único país da região com prevalência maior que 1 por 10 000 habitantes, representando 93,77% do total de casos. O Brasil e a República Dominicana mostraram um aumento na variação da prevalência durante 2011-2019, enquanto nos demais a tendência foi decrescente. A doença é mais frequente em homens e os casos multibacilares superam significativamente os paucibacilares. O Brasil apresentou as maiores incidências de hanseníase infantil e incapacidade de grau 2 durante o período avaliado. Conclusão: Na América Latina, a hanseníase só é considerada um problema de saúde pública no Brasil; no entanto, a maioria dos países da região continua notificando casos anualmente, revelando falta de assistência médica adequada. O presente estudo confirmou a importância da vigilância ativa, do diagnóstico precoce e do planejamento de ações contra a doença em todos os países avaliados, com o objetivo de reduzir e interromper a sua transmissão.

Comportamiento epidemiológico de la lepra en varios países de América Latina, 2011-2020

[RESUMEN]. Objetivo. Describir el comportamiento epidemiológico de la lepra en varios países latinoamericanos durante 2011-2020, tomando como base los indicadores de la Organización Mundial de la Salud (OMS). Método. Estudio transversal, descriptivo y cuantitativo con datos oficiales sobre incidencia y prevalencia en la población en general, niños, forma clínica y casos de discapacidad de grado 2 registrados por la OMS entre 2011 y 2020. Se seleccionaron los ocho países latinoamericanos con más casos y se realizaron análisis de estadística descriptiva simple y comparativa entre las variables. Resultados. Entre 2011-2020 se reportaron 301 312 casos de lepra en los países seleccionados: Argentina, Brasil, Colombia, Cuba, México, Paraguay, República Dominicana y Venezuela. Brasil fue el único con una prevalencia mayor a 1 por 10 000 habitantes y representó 93,77% de casos. En Brasil y República Dominicana se observó un aumento de la prevalencia durante 2011-2019, mientras que en los demás países esta tendió a disminuir. La enfermedad fue más frecuente en hombres, y los casos multibacilares superaron significativamente a los paucibacilares. En Brasil se encontraron las mayores incidencias de casos de lepra infantil y discapacidad de grado 2 durante el período evaluado. Conclusión. A pesar de que en América Latina la lepra solo es considerada un problema de salud pública en Brasil, la mayoría de los países de la región continúa reportando casos cada año, lo que revela una falta de atención médica adecuada. El estudio confirmó la importancia de la vigilancia activa, el diagnóstico temprano y la planificación de acciones contra la enfermedad en todos los países evaluados, con el propósito de disminuir o detener su transmisión.

[ABSTRACT]. Objective. To describe the epidemiological behavior of leprosy in several Latin American countries during 2011-2020, based on World Health Organization (WHO) indicators. Methods. Cross-sectional, descriptive and quantitative study with official data on incidence and prevalence in the general population, children, clinical form and cases with grade 2 disability from WHO records between 2011 and 2020. The eight countries in Latin America that reported most cases were selected and analyses were carried out using simple descriptive and comparative statistics between different variables. Results. During the study period, 301 312 cases of leprosy were reported in the selected countries: Argentina, Brazil, Colombia, Cuba, Dominican Republic, Mexico, Paraguay, and Venezuela. Brazil is the only country in the region with a prevalence greater than 1 per 10 000, representing 93.77% of all cases. Brazil and the Dominican Republic showed an increase in prevalence during 2011-2019, while in other countries the trend was decreasing. The disease is more frequent in men, and multibacillary cases significantly exceed paucibacillary ones. Brazil showed the highest incidences of cases of childhood leprosy and grade 2 disability during the evaluated period. Conclusion. In Latin America, leprosy is only considered a public health problem in Brazil; however, most countries in the region continue to report cases annually, revealing a lack of adequate medical care. This study confirmed the importance of active surveillance, early diagnosis and planning of actions against the disease in all the countries evaluated with the aim of reducing its transmission.

[RESUMO]. Objetivo. Descrever o comportamento epidemiológico da hanseníase em vários países de América Latina durante 2011-2020, tomando como base os indicadores da Organização Mundial da Saúde (OMS). Método. Estudo transversal, descritivo e quantitativo com dados oficiais de incidência e prevalência na população geral, em crianças, forma clínica e casos com incapacidade de grau 2 nos registros da OMS entre 2011 e 2020. Se selecionaram os oito países da América Latina que relataram a maioria dos casos e as análises foram avaliadas por meio de estatísticas descritivas e comparativas simples entre as variáveis. Resultados. No período, foram notificados 301 312 casos de hanseníase nos países selecionados: Argentina, Brasil, Colômbia, Cuba, México, Paraguai, República Dominicana e Venezuela. O Brasil é o único país da região com prevalência maior que 1 por 10 000 habitantes, representando 93,77% do total de casos. O Brasil e a República Dominicana mostraram um aumento na variação da prevalência durante 2011-2019, enquanto nos demais a tendência foi decrescente. A doença é mais frequente em homens e os casos multibacilares superam significativamente os paucibacilares. O Brasil apresentou as maiores incidências de hanseníase infantil e incapacidade de grau 2 durante o período avaliado. Conclusão. Na América Latina, a hanseníase só é considerada um problema de saúde pública no Brasil; no entanto, a maioria dos países da região continua notificando casos anualmente, revelando falta de assistência médica adequada. O presente estudo confirmou a importância da vigilância ativa, do diagnóstico precoce e do planejamento de ações contra a doença em todos os países avaliados, com o objetivo de reduzir e interromper a sua transmissão.

Comportamiento epidemiológico de la lepra en varios países de América Latina, 2011-2020 / Epidemiological behavior of leprosy in several Latin American countries, 2011-2020 / Comportamento epidemiológico da hanseníase em vários países da América Latina, 2011-2020

RESUMEN Objetivo. Describir el comportamiento epidemiológico de la lepra en varios países latinoamericanos durante 2011-2020, tomando como base los indicadores de la Organización Mundial de la Salud (OMS). Método. Estudio transversal, descriptivo y cuantitativo con datos oficiales sobre incidencia y prevalencia en la población en general, niños, forma clínica y casos de discapacidad de grado 2 registrados por la OMS entre 2011 y 2020. Se seleccionaron los ocho países latinoamericanos con más casos y se realizaron análisis de estadística descriptiva simple y comparativa entre las variables. Resultados. Entre 2011-2020 se reportaron 301 312 casos de lepra en los países seleccionados: Argentina, Brasil, Colombia, Cuba, México, Paraguay, República Dominicana y Venezuela. Brasil fue el único con una prevalencia mayor a 1 por 10 000 habitantes y representó 93,77% de casos. En Brasil y República Dominicana se observó un aumento de la prevalencia durante 2011-2019, mientras que en los demás países esta tendió a disminuir. La enfermedad fue más frecuente en hombres, y los casos multibacilares superaron significativamente a los paucibacilares. En Brasil se encontraron las mayores incidencias de casos de lepra infantil y discapacidad de grado 2 durante el período evaluado. Conclusión. A pesar de que en América Latina la lepra solo es considerada un problema de salud pública en Brasil, la mayoría de los países de la región continúa reportando casos cada año, lo que revela una falta de atención médica adecuada. El estudio confirmó la importancia de la vigilancia activa, el diagnóstico temprano y la planificación de acciones contra la enfermedad en todos los países evaluados, con el propósito de disminuir o detener su transmisión.

ABSTRACT Objective. To describe the epidemiological behavior of leprosy in several Latin American countries during 2011-2020, based on World Health Organization (WHO) indicators. Methods. Cross-sectional, descriptive and quantitative study with official data on incidence and prevalence in the general population, children, clinical form and cases with grade 2 disability from WHO records between 2011 and 2020. The eight countries in Latin America that reported most cases were selected and analyses were carried out using simple descriptive and comparative statistics between different variables. Results. During the study period, 301 312 cases of leprosy were reported in the selected countries: Argentina, Brazil, Colombia, Cuba, Dominican Republic, Mexico, Paraguay, and Venezuela. Brazil is the only country in the region with a prevalence greater than 1 per 10 000, representing 93.77% of all cases. Brazil and the Dominican Republic showed an increase in prevalence during 2011-2019, while in other countries the trend was decreasing. The disease is more frequent in men, and multibacillary cases significantly exceed paucibacillary ones. Brazil showed the highest incidences of cases of childhood leprosy and grade 2 disability during the evaluated period. Conclusion. In Latin America, leprosy is only considered a public health problem in Brazil; however, most countries in the region continue to report cases annually, revealing a lack of adequate medical care. This study confirmed the importance of active surveillance, early diagnosis and planning of actions against the disease in all the countries evaluated with the aim of reducing its transmission.

RESUMO Objetivo. Descrever o comportamento epidemiológico da hanseníase em vários países de América Latina durante 2011-2020, tomando como base os indicadores da Organização Mundial da Saúde (OMS). Método. Estudo transversal, descritivo e quantitativo com dados oficiais de incidência e prevalência na população geral, em crianças, forma clínica e casos com incapacidade de grau 2 nos registros da OMS entre 2011 e 2020. Se selecionaram os oito países da América Latina que relataram a maioria dos casos e as análises foram avaliadas por meio de estatísticas descritivas e comparativas simples entre as variáveis. Resultados. No período, foram notificados 301 312 casos de hanseníase nos países selecionados: Argentina, Brasil, Colômbia, Cuba, México, Paraguai, República Dominicana e Venezuela. O Brasil é o único país da região com prevalência maior que 1 por 10 000 habitantes, representando 93,77% do total de casos. O Brasil e a República Dominicana mostraram um aumento na variação da prevalência durante 2011-2019, enquanto nos demais a tendência foi decrescente. A doença é mais frequente em homens e os casos multibacilares superam significativamente os paucibacilares. O Brasil apresentou as maiores incidências de hanseníase infantil e incapacidade de grau 2 durante o período avaliado. Conclusão. Na América Latina, a hanseníase só é considerada um problema de saúde pública no Brasil; no entanto, a maioria dos países da região continua notificando casos anualmente, revelando falta de assistência médica adequada. O presente estudo confirmou a importância da vigilância ativa, do diagnóstico precoce e do planejamento de ações contra a doença em todos os países avaliados, com o objetivo de reduzir e interromper a sua transmissão.

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.