RESUMEN
BACKGROUND: Prior investigation has indicated a link between Hidradenitis suppurativa (HS) and cardiovascular diseases (CVDs), yet the causal relationship (CR) between these conditions remains unresolved. METHODS: This investigation utilized bidirectional Mendelian randomization (MR) analysis to determine the CR between HS and CVDs. Genetic instruments for both conditions were sourced from genome-wide association studies (GWAS). The GWAS summary data for CVD comprised coronary artery disease (CAD), myocardial infarction (MI), coronary atherosclerosis (CA), ischemic stroke (IS), and chronic heart failure (CHF). Four new approaches were added to the inverse variance weighted (IVW) method for the main analysis: weighted median, weighted MR-Egger, simple mode, and weighted mode. The validity of the causal conclusions was verified by sensitivity tests that included leave-one-out analysis, heterogeneity, and pleiotropy. RESULTS: HS and CAD (OR = 1.024; 95%CI: 1.002-1.046, P = 0.033), MI (OR = 1.001; 95%CI: 1.000-1.002, P = 0.033), and CA (OR = 1.001; 95%CI: 1.000-1.002, P = 0.022) were identified to have a positive CR, according to the IVW analysis. Conversely, no significant association was identified between HS and either IS or CHF. Furthermore, the bidirectional analysis indicated no reverse causation between these diseases. CONCLUSION: The findings of this study suggest a potential CR between HS and CAD, MI, and CA. Additional research is warranted to elucidate the biological mechanisms underlying these associations.
Asunto(s)
Enfermedades Cardiovasculares , Estudio de Asociación del Genoma Completo , Hidradenitis Supurativa , Análisis de la Aleatorización Mendeliana , Humanos , Hidradenitis Supurativa/genética , Enfermedades Cardiovasculares/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Acne vulgaris, rosacea, and hidradenitis suppurativa are enduring inflammatory skin conditions that frequently manifest with akin clinical attributes, posing a considerable challenge for their distinctive diagnosis. While these conditions do exhibit certain resemblances, they also demonstrate distinct underlying pathophysiological mechanisms and treatment modalities. Delving into both the molecular parallels and disparities among these three disorders can yield invaluable insights for refined diagnostics, effective management, and targeted therapeutic interventions. In this report, we present a comparative analysis of transcriptomic data across these three diseases, elucidating differentially expressed genes and enriched pathways specific to each ailment, as well as those shared among them. Specifically, we identified multiple zinc-binding proteins (SERPINA1, S100A7, S100A8, S100A9 and KRT16) as consistently highly upregulated genes across all three diseases. Our hypothesis suggests that these proteins could bind and sequester zinc, potentially leading to localized zinc deficiency and heightened inflammation. We identified high-dose dietary zinc as a promising therapeutic approach and confirmed its effectiveness through validation in an acne mouse model.
Asunto(s)
Acné Vulgar , Perfilación de la Expresión Génica , Hidradenitis Supurativa , Rosácea , Zinc , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/genética , Zinc/uso terapéutico , Zinc/metabolismo , Rosácea/tratamiento farmacológico , Rosácea/genética , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/genética , Animales , Ratones , Humanos , Proteína A7 de Unión a Calcio de la Familia S100/metabolismo , Proteína A7 de Unión a Calcio de la Familia S100/genética , Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , Transcriptoma , Proteínas S100/genética , Proteínas S100/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Modelos Animales de Enfermedad , Regulación hacia ArribaRESUMEN
Long noncoding RNAs (lncRNAs) have been demonstrated to be involved in biological processes, both physiological and pathological, including cancer, cardiovascular diseases, multiple sclerosis, autoimmune hepatitis and types I and II diabetes. LncRNAs are also known to have a critical role in the physiology of skin, and in the pathology of cutaneous diseases. LncRNAs are involved in a wide range of biological activities, including transcriptional posttranscriptional processes, epigenetics, RNA splicing, gene activation and or silencing, modifications and/or editing; therefore, lncRNAs may be useful as potential targets for disease treatment. Hidradenitis suppurativa (HS), also termed acne inversa, is a major skin disease, being an inflammatory disorder that affects ~1% of global population in a chronic manner. Its pathogenesis, however, is only partly understood, although immune dysregulation is known to have an important role. To investigate the biological relevance of lncRNAs with HS, the most differentially expressed lncRNAs and mRNAs were first compared. Furthermore, the lncRNAmicroRNA regulatory network was also defined via reverse transcriptionquantitative PCR analysis, whereby a trio of lncRNA expression signatures, lncRNATINCR, lncRNARBM5ASI1 and lncRNAMRPL23AS1, were found to be significantly overexpressed in patients with HS compared with healthy controls. In conclusion, the three lncRNAs isolated in the present study may be useful for improving the prognostic prediction of HS, as well as contributing towards an improved understanding of the underlying pathogenic mechanisms, thereby potentially providing new therapeutic targets.
Asunto(s)
Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Hidradenitis Supurativa , ARN Largo no Codificante , Humanos , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/sangre , ARN Largo no Codificante/genética , ARN Largo no Codificante/sangre , Masculino , Adulto , Femenino , MicroARNs/genética , MicroARNs/sangre , ARN Mensajero/genética , ARN Mensajero/metabolismo , Persona de Mediana Edad , Regulación de la Expresión GénicaRESUMEN
Hidradenitis suppurativa (HS) is an autoinflammatory skin disorder of the terminal hair follicle, which can present in sporadic, familial, or syndromic form. A classification has been proposed for the latter, distinguishing cases associated with a known genetic condition, with follicular keratinization disorders or with autoinflammatory diseases. This review focuses on the clinical and genetic features of those entities (ie, pyoderma gangrenosum [PG], acne and HS; PG, acne, pyogenic arthritis and HS; psoriatic arthritis, PG, acne and HS; synovitis, acne, pustulosis, hyperostosis, osteitis; and so forth) for which the collective term HS-related autoinflammatory syndromes is proposed.
Asunto(s)
Acné Vulgar , Artritis , Hidradenitis Supurativa , Hiperostosis , Osteítis , Piodermia Gangrenosa , Sinovitis , Humanos , Hidradenitis Supurativa/diagnóstico , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/terapia , Piodermia Gangrenosa/diagnóstico , Piodermia Gangrenosa/genética , Piodermia Gangrenosa/terapia , Osteítis/complicaciones , Acné Vulgar/diagnóstico , Acné Vulgar/genética , Acné Vulgar/complicaciones , Síndrome , Sinovitis/complicaciones , Hiperostosis/complicaciones , Artritis/complicacionesRESUMEN
Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disorder, which typically occurs during puberty or early adulthood. The pathogenesis of HS is complex and multifactorial; a close interaction between hormonal, genetic, epigenetics factors, host-specific aspects, and environmental influences contributes to the susceptibility, onset, severity, and clinical course of this disease, although the exact molecular mechanisms are still being explored. Epigenetics is currently emerging as an interesting field of investigation that could potentially shed light on the molecular intricacies underlying HS, but there is much still to uncover on the subject. The aim of this work is to provide an overview of the epigenetic landscape involved in HS. Specifically, in this in-depth review we provide a comprehensive overview of DNA methylation/hydroxymethylation, histone modifications, and non-coding RNAs (such as microRNA-miRNA-132, miRNA-200c, miRNA-30a-3p, miRNA-100-5b, miRNA-155-5p, miRNA-338-5p) dysregulation in HS patients. An interesting element of epigenetic regulation in HS is that the persistent inflammatory milieu observed in HS lesional skin could be exacerbated by an altered methylation profile and histone acetylation pattern associated with key inflammatory genes. Deepening our knowledge on the subject could enable the development of targeted epigenetic therapies to potentially restore normal gene expression patterns, and subsequentially ameliorate, or even reverse, the progression of the disease. By deciphering the epigenetic code governing HS, we strive to usher in a new era of personalized and effective interventions for this enigmatic dermatological condition.
Asunto(s)
Hidradenitis Supurativa , MicroARNs , Humanos , Adulto , Epigénesis Genética , Hidradenitis Supurativa/genética , MicroARNs/genética , Acetilación , Código de HistonasRESUMEN
La hidradenitis supurativa es un proceso inflamatorio crónico que en los últimos años ha adquirido una elevada importancia, por la subestimación de su prevalencia, y por tratarse de un proceso que produce una importante alteración en las relaciones interpersonales, de autoestima y de percepción de la imagen personal y de la imagen pública. A pesar de ser un proceso patológico de elevada importancia, por su repercusión no solo psicológica, sino también por su posible limitación física, que puede llegar incluso a reducir de forma definitiva la movilidad en este tipo de pacientes debido a la formación de cicatrices retráctiles en áreas de movilidad de las extremidades, las evidencias con respecto a su epidemiología y a su etiopatogenia eran hasta hace bien poco escasas. En la presente revisión se pretende analizar los últimos avances en el conocimiento de los diferentes aspectos epidemiológicos y clínicos de la hidradenitis supurativa. A su vez, se revisarán los diferentes sistemas de clasificación empleados actualmente en la evaluación de la gravedad de la enfermedad, así como la entrada de la ecografía cutánea como una técnica relevante en el seguimiento de este proceso inflamatorio crónico
Hidradenitis suppurativa is a chronic inflammatory disorder that has attracted increasing attention in recent years due to underestimations of prevalence and the considerable impact of the condition on interpersonal relationships, physical appearance, self-esteem, and body image. Although hidradenitis suppurative has a significant psychological impact on patients and can even cause physical limitations when thick scarring results in limb mobility limitation, until very recently little evidence was available relating to its epidemiology, etiology, or pathogenesis. In this review, we highlight the latest advances in our understanding of the epidemiological and clinical aspects of hidradenitis suppurativa. We will also look at the different classification systems for hidradenitis suppurativa and discuss the emergence of skin ultrasound as a promising technique for monitoring the course of this chronic inflammatory disease
Asunto(s)
Humanos , Masculino , Femenino , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/epidemiología , Hidradenitis Supurativa/fisiopatología , Factor de Necrosis Tumoral alfa , Inmunohistoquímica , Autoimagen , Relaciones Interpersonales , Comorbilidad , Hidradenitis Supurativa/etiología , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/patología , Microbiota/genética , Microbiota/fisiología , BiopelículasRESUMEN
OBJECTIVE: The aim of the present study was to assess the diagnostic value of a laser scanner developed to determine the coordinates of clinical bracket points and to compare with the results of a coordinate measuring machine (CMM). METHODS: This diagnostic experimental study was conducted on maxillary and mandibular orthodontic study casts of 18 adults with normal Class I occlusion. First, the coordinates of the bracket points were measured on all casts by a CMM. Then, the three-dimensional coordinates (X, Y, Z) of the bracket points were measured on the same casts by a 3D laser scanner designed at Shahid Beheshti University, Tehran, Iran. The validity and reliability of each system were assessed by means of intraclass correlation coefficient (ICC) and Dahlberg's formula. RESULTS: The difference between the mean dimension and the actual value for the CMM was 0.0066 mm. (95% CI: 69.98340, 69.99140). The mean difference for the laser scanner was 0.107 ± 0.133 mm (95% CI: -0.002, 0.24). In each method, differences were not significant. The ICC comparing the two methods was 0.998 for the X coordinate, and 0.996 for the Y coordinate; the mean difference for coordinates recorded in the entire arch and for each tooth was 0.616 mm. CONCLUSION: The accuracy of clinical bracket point coordinates measured by the laser scanner was equal to that of CMM. The mean difference in measurements was within the range of operator errors. .
OBJETIVO: o objetivo do presente estudo foi avaliar o valor diagnóstico de um scanner a laser desenvolvido para determinar as coordenadas dos pontos de colagem de braquetes, comparando seus resultados aos resultados obtidos com uma máquina de medição coordenada (MMC). MÉTODOS: esse estudo experimental diagnóstico foi conduzido com modelos ortodônticos obtidos a partir da arcada superior de 18 pacientes adultos, com oclusão normal de Classe I. Inicialmente, as coordenadas dos pontos de colagem de braquetes de todos os modelos foram mensuradas por uma MMC. Em seguida, as coordenadas tridimensionais (X, Y, Z) dos pontos foram mensuradas nos mesmos modelos por um scanner a laser 3D, desenvolvido na Universidade de Shahid Beheshti. A eficácia e confiabilidade dos dois sistemas foram avaliadas pelo Coeficiente de Correlação Intraclasse (CCI) e pela fórmula de Dahlberg. RESULTADOS: a diferença entre a média da dimensão mensurada pela MMC e o valor real obtido foi de 0,0066mm (IC 95%: 69,98340 - 69,99140). A diferença média para o scanner a laser foi de 0,107 ± 0,133 (95% IC: -0,002 - 0,24). Em cada método, as diferenças não foram significativas. Ao comparar os dois métodos, o CCI gerou um valor de 0,998 para a coordenada X e de 0,996 para a coordenada Y. A diferença média para as coordenadas registradas em cada dente da arcada foi de 0,616mm. CONCLUSÃO: a precisão das coordenadas do ponto de colagem dos braquetes foi a mesma no scanner a laser e na MMC. A diferença média entre as medições manteve-se dentro dos limites de erros operacionais. .