Phillygenin ameliorates nonalcoholic fatty liver disease via TFEB-mediated lysosome biogenesis and lipophagy.

BACKGROUND: Lipophagy is an autophagic process, which delivers the intracellular lipid droplets to the lysosomes for degradation. Recent studies revealed that the impairment of lysosomal biogenesis and autophagic flux led to dysregulation of lipophagy in hepatocytes, which exacerbated the development of nonalcoholic fatty liver disease (NAFLD). Therefore, agents restoring autophagic flux and lipophagy in hepatocytes may have therapeutic potential against this increasingly prevalent disease. Phillygenin (PHI), a lignin extracted from Forsythia suspense, exerts hepatoprotective and anti-inflammatory effects. However, the effect of PHI on NAFLD remains unknown. PURPOSE: This study aimed to investigate the protective effect of PHI on NAFLD and elucidate the underlying mechanism. METHODS: The effects of PHI were examined in palmitate (PA)-stimulated AML12 cells and primary hepatocytes, as well as in NAFLD mice induced by a high-fat diet (HFD). We also used transcription factor EB (TFEB) knockdown hepatocytes and hepatocyte-specific TFEB knockout (TFEBΔhep) mice for mechanistic studies. In vivo and in vitro studies were performed using western blots, immunofluorescence techniques, and transmission electron microscopy. RESULTS: Our results indicated that autophagic flux and lysosome biogenesis in PA-stimulated hepatocytes were impaired. PHI alleviated lipid deposition by increasing lysosomal biogenesis and autophagic flux. It also stimulated the release of endoplasmic reticulum Ca2+ to activate calcineurin, which regulated TFEB dephosphorylation and nuclear translocation, and promoted lysosomal biogenesis. In addition, PHI blocked the NLRP3 inflammasome pathway and improved hepatocyte inflammation in an autophagy-dependent manner. Consistent with the in vitro results, PHI improved hepatic steatosis and inflammation in HFD mice, but these beneficial effects were eliminated in hepatocyte-specific TFEB knockout mice. CONCLUSION: Despite PHI has been reported to have anti-hepatic fibrosis effects, whether it has a hepatoprotective effects against NAFLD and the underlying molecular mechanism remain unclear. Herein, we found that PHI restored lipophagy and suppressed lipid accumulation and inflammation by regulating the Ca2+-calcineurin-TFEB axis in hepatocytes. Thus, PHI represents a therapeutic candidate for the treatment of NAFLD.

Queratoconjuntivitis asociada a dermatitis atópica tratada con tocilizumab / Keratoconjunctivitis associated with atopic dermatitis treated with tocilizumab

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Tratamiento del liquen plano oral. Revisión sistemática y protocolo de actuación / Treatment of oral lichen planus. Systematic review and therapeutic guide

En la presente revisión sistemática se analizaron 55 artículos estructurados sobre la eficacia terapéutica frente al dolor y a los signos clínicos del liquen plano oral (LPO). La búsqueda bibliográfica se elaboró siguiendo los criterios del sistema PRISMA, seleccionando los ensayos realizados mediante alguno de los siguientes diseños metodológicos: entre fármaco (principio activo) vs. mismo fármaco en diferente excipiente o concentración, fármaco vs. diferente principio activo, fármaco vs. fitoterapia y fármaco vs. tratamiento con fototerapia. Basándonos en los resultados se propone un algoritmo que sirva de guía para establecer el tratamiento del LPO en sus formas clínicas atrófica y erosiva. Se destaca el empleo del propionato de clobetasol al 0,025-0,05% de aplicación tópica como primera alternativa terapéutica. En segundo lugar, el tacrolimús al 0,1% y pimecrolimús al 1% también formulado para su pauta tópica. Y, finalmente, se aborda el empleo de corticosteroide sistémico y la aplicación de láser de diodo (AU)

In this systematic review, 55 structured articles on the therapeutic efficacy against pain and clinical signs of oral lichen planus (OLP) were analysed. The literature search was developed according to the criteria of the PRISMA system, selecting the tests performed using one of the following methodological designs: drug (active ingredient) vs. drug in different excipient or concentration, drug vs. different active principle, drug vs. phytotherapy and drug vs. treatment with phototherapy. Based on the results, an algorithm is proposed to guide the treatment of OLP in its atrophic and erosive clinical forms. The use of clobetasol propionate at 0.025-0.05% of topical application as the first therapeutic alternative is highlighted. Secondly, 0.1% tacrolimus and 1% pimecrolimus also formulated for its topical regimen. And finally, we address the use of systemic corticosteroids and the application of diode lasers (AU)

Abordaje terapéutico en el eczema crónico de manos / Management of Chronic Hand Eczema

El manejo del eczema de manos es complejo, ya que engloba eczemas de etiopatogenia, curso y pronóstico muy diferentes; la mayoría de tratamientos disponibles no cuentan con niveles de eficacia establecidos, y en sus formas graves la calidad de vida se afecta de forma importante. La educación del paciente, las medidas de protección y el uso de emolientes constituyen un pilar fundamental en el abordaje de estos pacientes. Los corticoides tópicos de alta potencia son el tratamiento de elección, seguidos de los inhibidores de la calcineurina para el mantenimiento de la enfermedad. En los casos refractarios a estos tratamientos deberíamos utilizar la fototerapia o tratamientos sistémicos, los cuales no deberían demorarse para evitar sensibilizaciones, bajas laborales y alteración en la calidad de vida. La alitretinoína es el único tratamiento oral disponible que ha sido aprobado para su utilización en el eczema crónico de manos

Management of hand eczema is complex because of the broad range of different pathogeneses, courses, and prognoses. Furthermore, the efficacy of most available treatments is not well established and the more severe forms can have a major impact on the patient's quality of life. Patient education, preventive measures, and the use of emollients are the mainstays in the management of hand eczema. High-potency topical corticosteroids are the treatment of choice, with calcineurin inhibitors used for maintenance. Phototherapy or systemic treatments are indicated in patients who do not respond to topical treatments. Switching from topical treatments should not be delayed to avoid sensitizations, time off work, and a negative impact on quality of life. Alitretinoin is the only oral treatment approved for use in chronic hand eczema

Atopic dermatitis and alternative management strategies.

PURPOSE OF REVIEW: To discuss the significance of studies published over the previous year regarding the pathogenesis and treatment of atopic dermatitis, including prevention, skin care, environmental modifications, nutrition, education, and anti-inflammatory medications. RECENT FINDINGS: Recent evidence shows that 42.5% of the caregivers of children with atopic dermatitis had used alternative therapies, most commonly due to fears of topical steroid side-effects and dissatisfaction with conventional treatment. Common questions, such as the potential utility of prenatal probiotics for prevention of atopic dermatitis, as well as the interplay of food allergies and eczema will be discussed in detail. New research continues to show the efficacy and safety of topical calcineurin inhibitors and atopiclair. We will review advances in the understanding of the pathogenesis of atopic dermatitis, and the latest research on therapies available to clinicians to aid them in discussions with their patients. SUMMARY: Atopic dermatitis impacts negatively the quality of life of both patients and their families. General pediatricians play a pivotal role in the management of this chronic condition. Management should focus on providing sound advice and easing fears regarding topical steroids, as well as pursuing conservative treatments that have the potential to prevent flares.

New insights and therapies for teenage psoriasis.

PURPOSE OF REVIEW: Psoriasis is an important disorder in the adolescent population and has a tremendous physical and psychological impact on patients. It is important to understand the genetics, various clinical presentations, comorbidities, and treatment options associated with psoriasis. RECENT FINDINGS: The human leukocyte antigen-C gene likely contains a susceptibility locus for psoriasis. Cytokines interleukin-12 and interleukin-23 have been implicated in the pathogenesis of psoriasis as well. Psoriasis is likely associated with an increased risk of myocardial infarction, metabolic syndrome, Crohn's disease, and depression; it is difficult to assess the implications in the adolescent population. SUMMARY: Psoriasis is not rare in the adolescent population. It is important for physicians to be aware of the different clinical presentations as well as the spectrum of treatment options that are available.

Psoriasis en la infancia / Psoriasis in childhood

La psoriasis es una enfermedad crónica inflamatoria de la piel que afecta a un 2-3% de la población general. Aproximadamente, en uno de cada tres pacientes comienza en la edad infantil, y supone el 4% de todas las enfermedades de la piel del niño. La cara y las zonas de los pliegues se ven afectadas con frecuencia, y además son áreas especialmente sensibles a los efectos adversos de los corticoides tópicos. Los inhibidores de la calcineurina tópicos suponen una opción eficaz y segura en el tratamiento de la psoriasis invertida en niños(AU)

Psoriasis is a chronic inflammatory skin disorder that affects 2% to 3% of the population. Approximately one-third of the patients note its onset during childhood, and it accounts for 4%of the cutaneous disorders in children. The face and intertriginous areas are often involved, and they are particularly sensitive to the adverse effects of steroid use. Topical calcineurin inhibitors are an effective and safe option for the treatment of inverse psoriasis in children(AU)