RESUMEN
Generalized pustular psoriasis (GPP) is considered to be a distinct clinical entity from psoriasis vulgaris (PV), with different clinical and histological manifestations. The pathogenesis of GPP has not been thoroughly elucidated, especially in those patients lacking interleukin (IL)36RN. In present study, we performed RNA sequence analysis on skin lesions from 10 GPP patients (4 with and 6 without IL36RN mutation) and 10 PV patients without IL36RN mutation. Compared with PV, significantly overexpressed genes in GPP patients were enriched in IL-17 signalling pathway (MMP1, MMP3, DEFB4A and DEFB4B, etc.) and associated with neutrophil infiltration (MMP1, MMP3, ANXA and SERPINB, etc.). GPP with IL36RN mutations evidenced WNT11 upregulation and IL36RN downregulation in comparison to those GPP without IL36RN mutations. The expression of IL-17A/IL-36 in skin or serum and the origin of IL-17A in skin were also investigated. IL-17A expression in skin was significantly higher in GPP than PV patients, whereas, there were no differences in skin IL-36α/IL-36γ/IL-36RA or serum IL-17A/IL-36α/IL-36γ between GPP than PV. Besides, double immunofluorescence staining of MPO/IL-17A or CD3/IL-17A further confirmed that the majority of IL-17A in GPP skin was derived from neutrophils, but not T cells. These data emphasized the role of neutrophil-derived IL-17A in the pathogenesis of GPP with or without IL36RN mutations. Targeting neutrophil-derived IL-17A might be a promising treatment for GPP.
Asunto(s)
Psoriasis , Enfermedades Cutáneas Vesiculoampollosas , Humanos , Interleucina-17/genética , Interleucinas/genética , Interleucinas/metabolismo , Metaloproteinasa 1 de la Matriz , Metaloproteinasa 3 de la Matriz , Neutrófilos/metabolismo , Psoriasis/tratamiento farmacológicoRESUMEN
BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs with considerable morbidity and mortality. Immunomodulators for SJS/TEN including systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice. Emerging evidence suggested the therapeutic effects of tumor necrosis factor-α antagonists on SJS/TEN. OBJECTIVE: To compare the efficacy and safety of IVIG and systemic steroids in conjunction with or without etanercept, a tumor necrosis factor-α inhibitor, for patients with SJS/TEN. METHODS: We undertook a retrospective review of 41 patients with SJS/TEN admitted to our institution from 2015 to February 2021. A total of 25 patients with integrated data were involved in this study, of which 14 patients were treated with IVIG and corticosteroids and 11 were in addition given etanercept. The clinical characteristics, duration of hospitalization, exposure time to high-dose steroids, and the total amount of systemic steroids were analyzed. RESULTS: In comparison to conventional therapy, conjunction with etanercept reduced the duration of hospitalization (13.5 vs 19.0 days; P = .01), the exposure time of high-dose steroids (7.1 vs 14.9 days; P = .01), and the overall amount of systemic steroid (925 mg vs 1412.5 mg; P = .03) in patients with SJS/TEN. No pronounced adverse effects were observed within 6 months of follow-up after the treatment. CONCLUSION: The add-in of etanercept at the time of initiating conventional therapy could be a superior option to accelerate disease recovery and reduce the high dose and total amount of systemic steroids without pronounced adverse events in patients with SJS/TEN.
Asunto(s)
Etanercept , Síndrome de Stevens-Johnson , Corticoesteroides/uso terapéutico , Etanercept/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Estudios Retrospectivos , Esteroides/uso terapéutico , Síndrome de Stevens-Johnson/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
BACKGROUND: Wrinkle formation is the most visible characteristic of facial aging. Radiofrequency (RF) technology is currently utilized to reduce facial wrinkles and contribute to skin rejuvenation. OBJECTIVE: To analyze the efficacy and safety of a noninvasive, home-based RF device applied for facial rejuvenation in Chinese people. METHODS: A single-center, open-label, intraindividual controlled trial was performed on subjects who received an 8-week treatment of the RF device. A total of 22 female individuals aged 25-60 years with Fitzpatrick skin type III-IV were enrolled. Efficacy of treatment was subjectively evaluated using the Fitzpatrick Wrinkle Classification Scale (FWCS) assessed by physician or overall satisfaction of subject with a 10-point VAS, and objectively using the skin ultrasound examination as well as the 3D skin analysis system. Adverse event was recorded at each visit. RESULTS: In comparison with the baseline, evaluator-assessed FWCS scores showed significant improvement at 4 weeks (p < 0.005) and 8 weeks (p < 0.005) after treatment. All subjects reported different degrees of improvement in facial wrinkles after 8 weeks of treatment. The results of skin ultrasound examination revealed significant increase of the dermal thickness at week 8 (p < 0.05) as compared to the baseline. In addition, a significant decrease in the proportion and density of perioral wrinkles evaluated by the 3D skin analysis system was observed from baseline to week 4. The treatment was well-tolerated, and no serious adverse event was observed. CONCLUSION: This noninvasive, home-based RF device was effective in improving skin texture and elasticity with a safe and well-tolerated treating procedure.
Asunto(s)
Técnicas Cosméticas , Pueblos del Este de Asia , Terapia por Radiofrecuencia , Envejecimiento de la Piel , Femenino , Humanos , Técnicas Cosméticas/efectos adversos , Satisfacción del Paciente , Rejuvenecimiento , Resultado del Tratamiento , Adulto , Persona de Mediana Edad , AncianoRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that associates with aberrant activation of B lymphocytes and excessive autoantibodies. Interleukin 10 (IL-10)/interleukin 35 (IL-35) and IL-10/IL-35-producing regulatory B cells have been demonstrated to possess immunosuppressive functions during systemic lupus erythematosus. Here, we detected the proportion of CD19+CD24highCD27+ B cells as well as IL-10 and IL-35 levels in peripheral blood of SLE patients and healthy individuals, and investigated their relations with clinical features of SLE. METHODS: 41 SLE patients and 25 healthy controls were recruited. The patients were divided into groups based on SLEDAI score, anti-dsDNA antibody, rash, nephritis and hematological disorder. Flow cytometry was used to detect the proportion of CD24hiCD27+ B cells. ELISA was used to detect serum levels of IL-10 and IL-35. RESULTS: Our results showed that the CD19+CD24highCD27+ B population was decreased in active SLE patients, and anti-correlated with the disease activity. Of note, we found significant increase of IL-10 and decrease of IL-35 in SLE patients with disease activity score > 4, lupus nephritis or hematological disorders compared to those without related clinical features. CONCLUSIONS: Reduced CD19+CD24highCD27+ B cells expression may be involved in the pathogenesis of SLE. Moreover, we supposed that IL-35 instead of IL-10 played a crucial role in immune regulation during SLE disease.
Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Interleucina-10 , Antígenos CD19/metabolismo , Linfocitos B/metabolismo , Biomarcadores , Antígeno CD24/metabolismoRESUMEN
The defective MEK/ERK signaling pathway and downstream hypomethylation pattern of lymphocytes are crucial for the pathogenesis of systemic lupus erythematosus (SLE). However, the role that the mesenchymal stem cells play in the MEK/ERK signaling pathway and DNA methylation of peripheral blood mononuclear cells (PBMC) from SLE patients remains unknown. In this study, we found that the MEK/ERK signaling pathway of PBMC from SLE patients was activated after the coculture with bone marrow-derived mesenchymal stem cells (BM-MSC) compared with that from the control group. In addition, the expression level of DNA methyltransferase 1 (DNMT1) increased while the levels of CD70, integrin, alpha L (ITGAL), selectin-l, and IL-13 were reduced in PBMC from SLE patients. However, no obvious effect of BM-MSC on PBMC from healthy controls was observed. These findings revealed that BM-MSC might downregulate the expression of methylation-sensitive genes and then suppress the autoactivated PBMC via the MEK/ERK signaling pathway. And it may be one of the mechanisms that BM-MSC ameliorated SLE.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN/genética , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/enzimología , Lupus Eritematoso Sistémico/genética , Sistema de Señalización de MAP Quinasas , Células Madre Mesenquimatosas/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Técnicas de Cocultivo , HumanosRESUMEN
Neurofibromatosis type I is a rare neurocutaneous syndrome resulting from loss-of-function mutations of NF1. The present study sought to determine a correlation between mutation regions on NF1 and the risk of developing optic pathway glioma (OPG) in patients with neurofibromatosis type I. A total of 215 patients with neurofibromatosis type I, from our clinic or previously reported literature, were included in the study after applying strict inclusion and exclusion criteria. Of these, 100 patients with OPG were classified into the OPG group and 115 patients without OPG (aged ≥ 10 years) were assigned to the Non-OPG group. Correlation between different mutation regions and risk of OPG was analyzed. The mutation clustering in the 5' tertile of NF1 was not significantly different between OPG and Non-OPG groups (P = 0.131). Interestingly, patients with mutations in the cysteine/serine-rich domain of NF1 had a higher risk of developing OPG than patients with mutations in other regions [P = 0.019, adjusted odds ratio (OR) = 2.587, 95% confidence interval (CI) = 1.167-5.736], whereas those in the HEAT-like repeat region had a lower risk (P = 0.036, adjusted OR = 0.396, 95% CI = 0.166-0.942). This study confirms a new correlation between NF1 genotype and OPG phenotype in patients with neurofibromatosis type I, and provides novel insights into molecular functions of neurofibromin.