RESUMEN
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 a chronic inflammatory, immune-mediated, debilitating skin disease, characterized by subcutaneous nodules, with a still not clear pathophysiology. Although the prevalence is rather low (about 1% in Europe), its clinical complications, as well as the disabling symptomatology, make it necessary multidisciplinary therapeutic approaches. Not recently several authors described the involvement of the well-known gut-skin axis in both pathogenesis and progression of dermatological diseases. In particular, a high frequency of intestinal disorders (such as irritable bowel syndrome and inflammatory bowel disease) has been reported in HS patients, leading to speculate the existence of a relationship between such gut and skin diseases. The keystone in this relationship seems to be an impairment of the physiological gut mucosal barrier structure, resulting in the so-called leaky gut. The leaky gut, thus, might be responsible for a dietary compound-caused activation of the local immune system, with consequent trigging of both local and systemic inflammation, resulting in exacerbation of skin symptoms in HS patients. The current literature suggests the use of a low fermentable, oligo-, di, mono-saccharides and polyols (FODMAP) diet as a valid nutritional strategy in leaky gut. In light of this, we want to evaluate and consider the potential use of low-FODMAP diet in HS patient.
RESUMEN
Introduction: Hidradenitis suppurativa (HS) is a severe chronic skin disease. Although the pathogenesis remains unclear, at the basis of HS there is an enhancement of the immune and inflammatory response together with a susceptibility to environmental factors. Cytokine dysregulation is crucial in HS severity and progression. Objectives: The aim of this study was to analyze serum levels of different cytokines focusing on adiponectin concentration and its oligomers in HS patients compared to both obese and healthy subjects. Methods: The concentrations of adiponectin and cytokines were measured using enzyme-linked immunosorbent assay (ELISA); the oligomeric distribution of adiponectin (low molecular weight (LMW), medium molecular weight (MMW) and high molecular weight (HMW) oligomers)was evaluated through Western Blotting analysis. Results: Total adiponectin is statistically higher in HS patients compared to matched controls and obese subjects. Interestingly, Adiponectin oligomerization state is altered in HS, with an increase of HMW oligomers. Serum levels of PDGF-BB, IL-1ß, IL-5, Il-6, IL12, IL13, IL15, IL-17, GMCSF, INFγ, VEGF and MCP-1 are statistically higher while IL-1ra and RANTES levels are statistically lower in HS patients compared to healthy controls. Interestingly, adiponectin positively correlates with PDGF-BB, and IL-13. Conclusions: Our data confirmed that the complex network that links metabolism to immune homeostasis is dysregulated in HS and that adiponectin and its HMW oligomers are actively involved in this disease. In addition, the correlation between adiponectin and PDGF-BB, and IL-13 extends the role of this adipokine in modulation of the immune response, in particular regulating the innate immune system rather that the adaptive one. Further researches are needed to clarify the complex inflammatory milieu that characterizes HS syndrome.
RESUMEN
Hidradenitis suppurativa (HS) is a pathology characterized by chronic inflammation and skin lesions. The molecular basis of the inflammatory network remains unclear; however, since microRNAs (miRNAs) are involved in the modulation of inflammation, the composition of a micro-transcriptome RNA library using the blood of HS patients was analysed here. The total miRNA expression profiles of miRNAs from HS patients was assayed by real-time qPCR. Here, compared to healthy controls, miR-24-1-5p, miR-146a-5p, miR26a-5p, miR-206, miR338-3p, and miR-338-5p expression was found significantly different in HS. Knowing the significance of the miRNA mechanism in inflammatory and immune progression, we suggest that miRNA profiles found in HS patients can be significant in understanding the pathogenesis modality and establishing efficient biomarkers for HS early diagnosis. In particular, miR-338-5p was closely related to HS invasiveness and production of cytokines and was atypically overexpressed. miR-338-5p may represent a good promise as a non-invasive clinical biomarker for HS.
Asunto(s)
MicroARN Circulante , Hidradenitis Supurativa , MicroARNs , Biomarcadores , MicroARN Circulante/genética , Citocinas , Hidradenitis Supurativa/diagnóstico , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/patología , Humanos , Inflamación , MicroARNs/metabolismoRESUMEN
OBJECTIVE: To assess the efficacy of propionyl-carnitine (PC) in patients with type 2 diabetes and peripheral arterial disease (PAD). PATIENTS AND METHODS: This was an open pharmacodynamic study. Twenty-four obese patients with type 2 diabetes and PAD (stage IIb) were enrolled in the study. After an initial run-in period of 7 days on a low-calorie diet (1600 +/- 150 kcal/day), patients received intravenous PC (600mg in 100mL saline solution Na/K 0.9%) twice daily for 10 days (T1). RESULTS: Treatment with PC produced statistically significant increases in maximal walking distance (30%; p < 0.05) and initial claudication distance (15%; p < 0.05) in 15 and eight patients, respectively. In addition, a decrease in dosage of oral antihyperglycaemic agents was observed in 21 patients at T1. No PC-related adverse effects were reported. CONCLUSIONS: This study showed that acute intravenous administration of PC in patients with type 2 diabetes with PAD improved PAD-related symptoms as well as glycaemic control.