RESUMEN
Systemic sclerosis (SSc) is a rare autoimmune systemic disease that leads to decreased survival and quality of life due to fibrosis, inflammation, and vascular damage in the skin and/or vital organs. Early diagnosis is crucial for clinical benefit in SSc patients. Our study aimed to identify autoantibodies in the plasma of SSc patients that are associated with fibrosis in SSc. Initially, we performed a proteome-wide screening on sample pools from SSc patients by untargeted autoantibody screening on a planar antigen array (including 42,000 antigens representing 18,000 unique proteins). The selection was complemented with proteins reported in the literature in the context of SSc. A targeted antigen bead array was then generated with protein fragments representing the selected proteins and used to screen 55 SSc plasma samples and 52 matched controls. We found eleven autoantibodies with a higher prevalence in SSc patients than in controls, eight of which bound to proteins associated with fibrosis. Combining these autoantibodies in a panel could lead to the subgrouping of SSc patients with fibrosis. Anti-Phosphatidylinositol-5-phosphate 4-kinase type 2 beta (PIP4K2B)- and anti-AKT Serine/Threonine Kinase 3 (AKT3)-antibodies should be further explored to confirm their association with skin and lung fibrosis in SSc patients.
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Enfermedades Autoinmunes , Fibrosis Pulmonar , Esclerodermia Sistémica , Humanos , Autoanticuerpos , Enfermedades Autoinmunes/complicaciones , Fibrosis , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Proteínas Proto-Oncogénicas c-akt , Fibrosis Pulmonar/complicaciones , Calidad de Vida , Esclerodermia Sistémica/complicacionesRESUMEN
The aim of this study was to assess the knowledge and influence of predatory journals in the field of dermatology in Austria. A total of 286 physicians (50.5% men) completed a questionnaire. The vast majority of subjects read scientific articles (n = 281, 98.3%) and took them into consideration in their clinical decision-making (n = 271, 98.5% of participants that regularly read scientific literature). Open access was known by 161 (56.3%), predatory journals by 84 (29.4%), and the Beall's list by 19 physicians (6.7%). A total of 117 participants (40.9%) had been challenged by patients with results from the scientific literature, including 9 predatory papers. Participants who knew of predatory journals had a higher level of education as well as scientific experience, and were more familiar with the open-access system (p < 0.001). These results indicate that the majority of dermatologists are not familiar with predatory journals. This is particularly the case for physicians in training and in the early stages of their career.
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Actitud del Personal de Salud , Dermatólogos/psicología , Conocimientos, Actitudes y Práctica en Salud , Publicación de Acceso Abierto , Publicaciones Periódicas como Asunto , Adulto , Austria , Toma de Decisiones Clínicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Publicación de Acceso Abierto/economía , Publicación de Acceso Abierto/ética , Publicaciones Periódicas como Asunto/economía , Publicaciones Periódicas como Asunto/ética , Estudios Prospectivos , Mala Conducta CientíficaAsunto(s)
Necrosis Grasa , Paniculitis , Enfermedades de la Piel , Deficiencia de alfa 1-Antitripsina , Absceso , HumanosRESUMEN
The treatment of chronic inflammatory skin disease is associated with the use of topical corticosteroids. Their efficacy, tolerability and adverse effects depend on several factors, specifically potency, type of preparation, extemporaneous dilutions, quantity used, magnitude of the treated body surface, frequency of application, location, patient age, method of application and condition of the skin barrier. We report on two men suffering from chronic inflammatory skin disease, who presented with fatigue and cushingoid appearance after prolonged self-application of potent corticosteroids. Impairment of the skin barrier due to their underlying skin disease, frequent self-application of topical steroids and repeated application of the entire body led to extensive absorption of these substances, eventually culminating in the suppression of the pituitary-hypothalamic-adrenal axis. In conclusion, topical corticosteroids are effective and well-established therapeutic modalities. However, inappropriate use of topical corticosteroids can cause side effects.
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Insuficiencia Suprarrenal/inducido químicamente , Betametasona/análogos & derivados , Síndrome de Cushing/inducido químicamente , Glucocorticoides/efectos adversos , Automedicación/efectos adversos , Administración Cutánea , Adulto , Betametasona/administración & dosificación , Betametasona/efectos adversos , Enfermedad Crónica , Dermatitis Atópica/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Humanos , Masculino , Psoriasis/tratamiento farmacológico , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Lupus erythematosus (LE) is a systemic autoimmune disease. However, some patients have only cutaneous LE (CLE), whereas others develop internal organ involvement. Ro/SS-A antibodies are frequently detected in photosensitive variants of LE. OBJECTIVE: The prevalence of LE-specific and LE-nonspecific cutaneous manifestations and their relation to internal organ involvement in Ro/SS-A antibody-positive patients were investigated. METHODS: All Ro/SS-A-positive patients between January 2000 and December 2011 were reviewed. Only patients with Ro/SS-A antibodies and LE were enrolled and retrospectively analyzed. RESULTS: In all, 215 Ro/SS-A antibody-positive patients were given the diagnosis of LE. Older patients (>50 years old) presenting with subacute CLE or chronic CLE and negative antinuclear antibody usually only experienced skin involvement. In contrast, internal organ involvement was observed in younger patients (<50 years old) with subacute CLE or chronic CLE presenting with the clinical and laboratory markers: fatigue, positive antinuclear antibody, and additional extractable nuclear antigen. Young female patients with acute CLE should be recognized as a separate subset of Ro/SS-A antibody-positive patients because almost a third was given the diagnosis of kidney involvement. Logistic regression analysis revealed that internal organ involvement was observed in patients with LE presenting with LE-nonspecific cutaneous manifestations, arthralgia, leukopenia, positive antinuclear antibody, and fatigue. LIMITATIONS: This was a retrospective study from a single referral center specializing in dermatologic diseases. CONCLUSION: The particular cutaneous variant of LE and age at Ro/SS-A detection predict different risks for internal organ involvement in Ro/SS-A antibody-positive patients with LE.
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Anticuerpos Antinucleares/análisis , Lupus Eritematoso Cutáneo/inmunología , Lupus Eritematoso Sistémico/inmunología , Piel/inmunología , Adulto , Femenino , Humanos , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The phenotypes and functions of endothelial cells (EC), a heterogeneous cell population, vary along the vascular tree and even in the same organ between different vessels. The placenta is an organ with abundant vessels. To enhance further knowledge concerning placenta derived EC, we develop a new method for isolation, purification and culture of these EC. Moreover, in order to investigate the peculiarity of placenta derived EC we compare their phenotypic and functional characteristics with human dermal lymphatic endothelial cells (HDLEC) and human umbilical vein endothelial cells (HUVEC). Freshly isolated placenta derived EC displayed an elongated shape with pale cytoplasm and showed the typical cobblestone pattern of EC but also a swirling pattern when confluent. FISH-analyses of the isolated EC from placentae of male fetus revealed an XY genotype strongly indicating their fetal origin. Characterisation of placenta derived fetal EC (fEC) underlined their blood vessel phenotype by the expression of vWF, Ulex europaeus lectin-1, HLA-class I molecules, CD31, CD34, CD36, CD51/61, CD54, CD62E, CD105, CD106, CD133, CD141, CD143, CD144, CD146, VEGFR-1, VEGFR-2, EN-4, PAL-E, BMA120, Tie-1, Tie-2 and α-Tubulin. In contrast to previous reports the expression of lymphatic markers, like VEGFR-3, LYVE-1, Prox-1 and Podoplanin was consistently negative. Haematopoietic surface markers like CD45 and CD14 were also always negative. Various functional tests (Dil-Ac-LDL uptake, Matrigel assay and TNF-α induced upregulation of CD62E and CD54) substantiated the endothelial nature of propagated fEC. At the ultrastructural level, fEC harboured numerous microvilli, micropinocytic vesicles at their basis, were rich in intermediate filaments and possessed typical Weibel - Palade bodies. In conclusion, the placenta is a plentiful source of fetal, microvascular, blood EC with an expression profile (CD34+, CD133+, VEGFR-2+, CD45-) suggestive of an endothelial progenitor phenotype.
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Antígenos CD/metabolismo , Biomarcadores/metabolismo , Células Endoteliales/citología , Placenta/irrigación sanguínea , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Antígeno AC133 , Adulto , Antígenos CD34/metabolismo , Técnicas de Cultivo de Célula , Células Cultivadas , Estructuras Citoplasmáticas/ultraestructura , Dermis/irrigación sanguínea , Células Endoteliales/metabolismo , Células Endoteliales/ultraestructura , Femenino , Glicoproteínas/metabolismo , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Antígenos Comunes de Leucocito/metabolismo , Microvellosidades/ultraestructura , Péptidos/metabolismo , Embarazo , Nacimiento a TérminoRESUMEN
Dendritic cells (DCs) critically regulate immune responses and the "immune-surveillance" of tumours. This study retrospectively analysed the distribution and maturation status of DC-subsets in T-cell lymphoma of the skin. Mycosis fungoides and Sézary syndrome (n = 25) were investigated immunohistochemically for DC subsets, based on C-type lectin receptor expression: Langerhans' cells (langerin/CD207+, DEC-205/CD205+), dermal DCs (DC-SIGN/CD209+, CD205+) and plasmacytoid DC (BDCA-2/CD303+). Maturation status was assessed by double-labelling for CD83 and CD208/DC-LAMP. DCs were interspersed between the neoplastic infiltrate, and a marked increase in numbers of all three subsets was noted, DC-SIGN+ dermal DCs constituting the majority. Substantial numbers of plasmacytoid DCs were consistently observed. Most DCs in epidermis and dermis were phenotypically immature. Amongst the relatively few mature DCs in the dermis, langerin+ cells predominated. There was a positive correlation between the histological intensity of the tumour infiltrate and DC numbers. It is possible that mature DCs reflect ongoing anti-tumour immune responses, and immature DCs the induction of tumour tolerance.
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Células Dendríticas/metabolismo , Células Dendríticas/patología , Micosis Fungoide/patología , Síndrome de Sézary/patología , Neoplasias Cutáneas/patología , Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Humanos , Inmunoglobulinas/metabolismo , Células de Langerhans/metabolismo , Células de Langerhans/patología , Lectinas Tipo C/metabolismo , Proteína 3 de la Membrana Asociada a Lisosoma/metabolismo , Glicoproteínas de Membrana/metabolismo , Antígenos de Histocompatibilidad Menor , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/metabolismo , Estudios Retrospectivos , Antígeno CD83RESUMEN
Systemic sclerosis (SSc) is a rare systemic autoimmune disorder marked by high morbidity and increased risk of mortality. Our study aimed to analyze metabolomic profiles of plasma from SSc patients by using targeted and untargeted metabolomics approaches. Furthermore, we aimed to detect biochemical mechanisms relevant to the pathophysiology of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry technology. The investigation of plasma samples from SSc patients (n = 52) compared to a control group (n = 48) allowed us to identify four different dysfunctional metabolic mechanisms, which can be assigned to the kynurenine pathway, the urea cycle, lipid metabolism, and the gut microbiome. These significantly altered metabolic pathways are associated with inflammation, vascular damage, fibrosis, and gut dysbiosis and might be relevant for the pathophysiology of SSc. Further studies are needed to explore the role of these metabolomic networks as possible therapeutic targets of SSc.
RESUMEN
BACKGROUND: Chondrodermatitis nodularis chronica helicis is a rather common condition which substantially affects quality of life causing pain and sleeping disturbances. Surgical treatment is connected with a tendency to recurrence. Mechanical pressure is probably the main etiological factor. PATIENTS AND METHODS: A prospective study was performed with 18 patients that were offered a non-surgical treatment using a self-made bandage of foam plastic which they applied during the night. Of these, 12 performed the treatment including follow-up; 6 patients initially also consented, but they did not return after the initial visit. RESULTS: 11 patients reported substantial reduction of pain within the first month; after an average of 1.75 months they were free of pain. All 8 patients with initial sleeping problems caused by pain reported undisturbed sleep after only one month. In 11 patients the lesions receded satisfactorily, in 9 patients completely, in 2 patients leaving small asymptomatic residual lesions. Recurrences appeared in 3 patients with 2 of them having been surgically pretreated at the same location. CONCLUSIONS: We recommend conservative treatment using protective padding as first line treatment for chondrodermatitis nodularis chronica helicis. The successful outcome achieved only by relief of pressure supports pressure as the main etiological factor in the development of the disease.
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Enfermedades de los Cartílagos/diagnóstico , Enfermedades de los Cartílagos/cirugía , Descompresión Quirúrgica/métodos , Dermatitis/diagnóstico , Dermatitis/cirugía , Enfermedades del Oído/diagnóstico , Enfermedades del Oído/cirugía , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome , Resultado del TratamientoRESUMEN
Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.
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Context: Immune-related adverse events frequently take place after initiation of immune checkpoint inhibitors (ICI) therapy. The thyroid gland is the endocrine organ most commonly affected by ICI therapy, the pathological mechanism is still poorly understood. Case Description: A 60-year old Upper Austrian male melanoma patient under pembrolizumab therapy received thyroidectomy because of a suspicious FDG avid thyroid nodule. Histopathology showed a pattern comparable with thyroiditis de Quervain. The inflammatory process consisted predominantly of T lymphocytes with a dominance of CD4+ T helper cells. In addition CD68+ histiocytes co-expressing PD-L1 were observed. Conclusion: Clusters of perifollicular histiocytes expressing PD-L1 were observed in this case of pembrolizumab induced thyroiditis - probably induced by the former ICI therapy. This finding might indicate the initial target for the breakdown of self tolerance. In context with other data the immunological process seems to be driven by CD3+ lymphocytes infiltrating the thyroid.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Antígeno B7-H1/metabolismo , Linfocitos T CD4-Positivos/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Histiocitos/inmunología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/métodos , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Glándula Tiroides/patología , Tiroiditis/diagnóstico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Movimiento Celular , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Melanoma/complicaciones , Melanoma/diagnóstico , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/diagnóstico , Glándula Tiroides/inmunología , Tiroidectomía , Tiroiditis/etiologíaRESUMEN
Background: Little is known about the real-time cause-effect relations between IL-6 concentrations and SLE symptoms. Methods: A 52-year-old woman with mild SLE activity collected her entire urine for the determination of IL-6/creatinine and protein/creatinine levels (ELISA, HPLC) for a period of 56 days in 12 h intervals (total: 112 measurements). Additionally, she answered questionnaires (VAS) on oral ulceration, facial rash, joint pain, fatigue and tiredness and measured her temperature orally twice a day. Time-series analyses consisted of ARIMA modeling and cross-correlational analyses (one lag = 12 h, significance level = p < 0.05). Results: Statistical analyses showed that increased urinary IL-6 concentrations preceded increased urinary protein levels by 36-48 h (lag3: r=+.225; p=.017) and that, in the opposite direction of effect, increased urinary protein preceded urinary IL-6 decreases by 12-24 h (lag1: r=-.322; p<.001). Moreover, urinary IL-6 increases co-occurred with increased oral ulceration (lag0: r=+.186; p=.049); after 48-60 h, however, IL-6 increases showed a strong tendency to precede oral ulceration decreases (lag4: r=-.170; p=.072). Increases in facial rash preceded decreases in urinary IL-6 after 84-96 h (lag7: r=-.215; p=.023). As to fatigue, increases in urinary IL-6 co-occurred with decreased fatigue (lag0: r=-.193; p=.042); after 84-96 h, however, IL-6 increases preceded fatigue increases (+lag7: r=+.189; p=.046). Finally, joint pain, tiredness and body temperature did not significantly correlate with urinary IL-6 concentrations in either direction of effect. Conclusions: The results of this evaluation point to real-life feedback mechanisms between immune activity and SLE symptoms. Comparison with a previous evaluation of this patient suggests a counterregulatory mechanism between Th1 activity and IL-6. These findings are preliminary and require replication to draw firm conclusions about the real-time relation between IL-6 and SLE disease activity.
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Artralgia/etiología , Dermatosis Facial/etiología , Fatiga/etiología , Fiebre/etiología , Interleucina-6/orina , Lupus Eritematoso Sistémico/orina , Úlceras Bucales/etiología , Proteinuria/etiología , Causalidad , Creatinina/orina , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Persona de Mediana Edad , Evaluación de SíntomasAsunto(s)
Amiloidosis/patología , Neoplasias Cutáneas/patología , Piel/patología , Biopsia , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disease caused by mutations in the AIRE gene. We report the case of a female patient with a 967-979del13 mutation in the AIRE gene. Her medical history included autoimmune hypoparathyroidism, Addison disease, and chronic mucocutaneous candidiasis. At the age of 40, she developed multiple white verrucous plaques on the oral mucosa. Histologically, the lesions appeared as moderately differentiated squamous cell carcinomas. The patient subsequently developed multiple local recurrences and therefore required repeated surgery. Notably, a higher incidence rate of oral and esophageal squamous cell carcinoma has been observed in this syndrome. However, the critical pathogenetic pathways implicated in squamous cell carcinoma development in APECED are far from being well understood.
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Candidiasis Mucocutánea Crónica/etiología , Carcinoma de Células Escamosas/etiología , Poliendocrinopatías Autoinmunes/complicaciones , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Candidiasis Mucocutánea Crónica/tratamiento farmacológico , Femenino , Humanos , Nistatina/uso terapéuticoRESUMEN
The existence of endothelial progenitor cells (EPC) with high cell-cycle rate in human umbilical cord blood has been recently shown and represents a challenging strategy for therapeutic neovascularization. To enhance knowledge for future cellular therapy, we compared the phenotypic, functional and gene expression differences between EPC-derived cells generated from cord blood CD34(+) cells, and lymphatic and macrovascular endothelial cells (EC) isolated from human foreskins and umbilical veins, respectively. Under appropriate culture conditions, EPC developed into fully matured EC with expression of similar endothelial markers as lymphatic and macrovascular EC, including CD31, CD36, von Willebrand factor FVIII, CD54 (ICAM-1), CD105 (endoglin), CD144 (VE-cadherin), Tie-1, Tie-2, VEGFR-1/Flt-1 and VEGFR-2/Flk-1. Few EPC-derived cells became positive for LYVE-1, indicating their origin from haematopoietic stem cells. However they lacked expression of other lymphatic cell-specific markers such as podoplanin and Prox-1. Functional tests demonstrated that the cobblestone EPC-derived cells up-regulated CD54 and CD62E expression in response to TNF-alpha, incorporated DiI-acetylated low-density liproprotein and formed cord- and tubular-like structures with capillary lumen in three-dimensional collagen culture--all characteristic features of the vascular endothelium. Structures compatible with Weibel-Palade bodies were also found by electron microscopy. Gene microarray profiling revealed that only a small percentage of genes investigated showed differential expression in EPC-derived cells and lymphatic EC. Among them were adhesion molecules, extracellular matrix proteins and cytokines. Our data point to the close lineage relationship of both types of vascular cells and support the theory of a venous origin of the lymphatic system.
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Antígenos CD34/metabolismo , Antígenos CD/metabolismo , Células Endoteliales/citología , Células Endoteliales/metabolismo , Perfilación de la Expresión Génica , Glicoproteínas/metabolismo , Vasos Linfáticos/citología , Péptidos/metabolismo , Células Madre/citología , Antígeno AC133 , Diferenciación Celular , Forma de la Célula , Células Cultivadas , Niño , Preescolar , Regulación hacia Abajo , Células Endoteliales/ultraestructura , Sangre Fetal/citología , Humanos , Lactante , Recién Nacido , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Células Madre/metabolismo , Células Madre/ultraestructura , Regulación hacia Arriba , Cuerpos de Weibel-Palade/ultraestructuraRESUMEN
Epithelial-to-mesenchymal transition (EMT) is critical for embryonic development and wound healing, and occurs in fibrotic disease and carcinoma. Here, we show that EMT also occurs within the bulge, the epithelial stem cell (eSC) niche of human scalp hair follicles, during the inflammatory permanent alopecia, lichen planopilaris. We show that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with transforming growth factor-ß1, epidermal growth factor, and IFN-γ administration, which to our knowledge has not been reported previously. Moreover, induction of EMT within primary human eSCs can be prevented and even partially reversed ex vivo by peroxisome proliferator-activated receptor-γ agonists, likely through suppression of the transforming growth factor-ß signaling pathway. Furthermore, we show that peroxisome proliferator-activated receptor-γ agonists also attenuates the EMT signature even in lesional lichen planopilaris hair follicles ex vivo. We introduce lichen planopilaris as a model disease for pathological EMT in human adult eSCs, report a preclinical assay for therapeutically manipulating eSC EMT within a healthy human (mini-)organ, and show that peroxisome proliferator-activated receptor-γ agonists are promising agents for suppressing and partially reversing EMT in human hair follicles eSCs ex vivo, including in lichen planopilaris.
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Transición Epitelial-Mesenquimal , Liquen Plano/patología , Células Madre Mesenquimatosas/patología , Adulto , Anciano , Células Cultivadas , Femenino , Humanos , Queratina-15/análisis , PPAR gamma/fisiología , Peroxisomas/efectos de los fármacos , Pioglitazona/farmacología , Nicho de Células MadreAsunto(s)
Mejilla , Dirofilaria/aislamiento & purificación , Dirofilariasis/diagnóstico , Edema/parasitología , Mordeduras y Picaduras de Insectos/complicaciones , Viaje , Albendazol/uso terapéutico , Animales , Biopsia , Mejilla/parasitología , Mejilla/patología , Dirofilaria/genética , Dirofilariasis/tratamiento farmacológico , Femenino , Filaricidas/uso terapéutico , Humanos , Italia , Persona de Mediana EdadRESUMEN
BACKGROUND: This integrative single-case study investigated the 12 h-to-12 h cause-effect relations between 55 kD soluble tumor necrosis factor receptor type 1 (sTNF-R55) and specific and unspecific symptoms in a 52-year-old Caucasian woman with mild systemic lupus erythematosus (SLE) disease activity. METHODS: The patient collected her entire urine for 56 days in 12 h-intervals to determine sTNF-R55/creatinine and protein/creatinine levels (ELISA, HPLC). Additionally, twice a day, she took notes on oral ulceration and facial rash; answered questionnaires (VAS) on fatigue, weakness, and joint pain; and measured body temperature orally. Time series analysis consisted of ARIMA modeling and cross-correlational analyses (significance level = p < 0.05). RESULTS: Time series analysis revealed both a circadian and a circasemiseptan rhythm in the urinary sTNF-R55 data. Moreover, several significant lagged correlations between urinary sTNF-R55 concentrations and SLE symptoms in both directions of effect were identified. Specifically, increased urinary sTNF-R55 concentrations preceded decreased urinary protein levels by 36-48 h (r = -0.213) and, in the opposite direction of effect, increased protein levels preceded increased sTNF-R55 concentrations by 24-36 h (r = +0.202). In addition, increased urinary sTNF-R55 levels preceded increased oral ulcers by 36-48 h (r = +0.277) and, conversely, increased oral ulceration preceded decreased sTNF-R55 levels by 36-48 h (r = -0.313). Moreover, increased urinary sTNF-R55 levels preceded decreased facial rash by 36-48 h (r = -0.223) and followed increased body temperature after 36-48 h (r = +0.209). Weakness, fatigue and joint pain were not significantly correlated with urinary sTNF-R55 levels. CONCLUSIONS: This study gathered first evidence of real-life, long-term feedback loops between cytokines and SLE symptoms in mild SLE disease activity. Such insights into the potential role of sTNF-R55 in SLE would not have been possible had we applied a pre-post design group study. These findings require replication before firm conclusions can be drawn.