Cinnamtannin D1 ameliorates DSS-induced colitis by preventing Th17/Treg imbalance through activation of the AMPK/mTOR pathway

Background: Inflammatory bowel disease (IBD) is a chronic idiopathic gastrointestinal dis-ease, including ulcerative colitis (UC) and Crohn’s disease (CD), which is typically charac-terized by chronicity and relapse. Cinnamtannin D1 (CTD1), extracted from Cinnamomum tamala, has been found to exert good immunosuppressive activity. However, the role of CTD1 in IBD is unclear. Methods: The colitis mice model was established by dextran sulfate sodium (DSS) treat-ment. Protein levels (p-STAT3/STAT3, ROR-γt, p-STAT5/STAT5, FOXP3, p-AMPK/AMPK, and p-mTOR/mTOR) were examined using Western blotting analysis. Changes in histopathol-ogy were detected through hematoxylin and eosin staining. The proportion of T helper 17 (Th17) cells and regulatory T (Treg) cells was measured by flow cytometry analysis.Results: CTD1 improved body weight and colon length, and alleviated inflammation and histological damage in DSS-induced colitis mice model. DSS treatment also demonstrated a negative effect on Th17–Treg cells balance whereas CTD1 restored the balance of Th17–Treg cells in DSS-induced colitis mice model. Regulatory factors (such as STAT3, ROR-γt, STAT5, and FOXP3) that closely related to the balance of Th17–Treg cells were regulated by CTD1. In addition, AMPK phosphorylation was increased and mTOR phosphorylation was inhibited by CTD1 in DSS-induced colitis mice model. Conclusion: These findings established that CTD1 improved DSS-induced colitis by suppress-ing Th17–Treg cells balance by activating the AMPK/mTOR pathway. This study provided a new strategy for developing novel treatments for patients with IBD (AU)

Inhibidores de JAK: usos en dermatología. Parte 2: aplicaciones en psoriasis, dermatitis atópica y otras dermatosis / Janus Kinase Inhibitors in Dermatology: Part 2: Applications in Psoriasis, Atopic Dermatitis, and Other Dermatoses

La vía de señalización de citocinas Janus cinasa/transductor de señal y activador de transcripción (JAK/STAT) es un área de interés emergente en dermatología, con evidencia creciente del papel clave en la patogénesis de las enfermedades inflamatorias cutáneas. Debido a que algunas citocinas proinflamatorias usan la vía JAK/STAT para la transducción de señales se convierte en una diana terapéutica prometedora para el tratamiento de dichas enfermedades al modular de forma selectiva el sistema inmune. El objetivo de esta revisión es conocer la vía de señalización JAK/STAT y su papel en distintas enfermedades dermatológicas inmunomediadas. En esta segunda parte, se revisará la eficacia y seguridad de los inhibidores de JAK –en formulación oral o tópica– para el tratamiento de la psoriasis, la dermatitis atópica y otras dermatosis (AU)

Dermatologists’ interest in the Janus-associated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway has been growing as evidence builds to support its key role in the pathogenesis of inflammatory skin diseases. Because certain proinflammatory cytokines use the JAK/STAT pathway for signal transduction, it has become a promising therapeutic target in diseases where selective modulation of the immune system can be useful. We aim to review current knowledge of the JAK/STAT signaling pathway and its role in immune-mediated skin diseases. In the second part of the review we cover the efficacy and safety of oral and topical JAK inhibitors in the treatment of psoriasis, atopic dermatitis, and other skin diseases (AU)

Síndrome de hipergammaglobulinemia IgE con infecciones recurrentes: patogénesis, diagnóstico y aproximación terapéutica / Hyper-IgE recurrent infection syndrome: pathogenesis, diagnosis and therapeutic management

El síndrome de la hipergammaglobulinemia IgE con infecciones recurrentes es una inmunodeficiencia primaria poco frecuente, que se caracteriza por niveles elevados de IgE, dermatitis eccematoide, infecciones recurrentes de piel y pulmón por Staphylococcus aureus, y formación de abscesos con escasos signos inflamatorios. También produce alteraciones dentarias, esqueléticas y del tejido conjuntivo. La forma clásica (tipo 1) está causada por mutaciones dominantes del gen de la proteína transductora de señal y activadora de la transcripción 3. Se ha descrito una forma incompleta (tipo 2) solo con las manifestaciones de la inmunodeficiencia, pero sin manifestaciones mesenquimales. Esta forma incompleta se debe a la mutación recesiva del gen de la tirosin-cinasa 2. Ambas mutaciones condicionan un déficit en la generación de células Th17 a partir de células T CD4+. Estos avances en el conocimiento genético e inmunológico del síndrome de hipergammaglobulinemia IgE han permitido la mejor comprensión de los fenómenos clínicos de la enfermedad(AU)

Hyper-IgE recurrent infection syndrome is an uncommon primary immunodeficiency characterized by high serum levels of total IgE, eczema-like dermatitis, recurrent skin abscesses and staphylococci pneumonias, which can produce abscesses with mild inflammatory signs. It also causes dental, musculoskeletal and connective tissue abnormalities. The classical (type 1) variation is caused by autosomal-dominant mutations in signal transducer and activator of transcription 3. An incomplete form (type 2) has been described with only the immunological manifestations, but without the mesenchymal manifestations, has been described. This incomplete form is caused by recessive mutations in the tyrosine kinase 2 gene. Both kinds of mutations produce deficient formation of Th17-cells. These advances in the genetic and immunologic knowledge of hyper-IgE recurrent infection syndrome have allowed a better clinical comprehension of the clinical phenomena of the disease(AU)

Proapoptotic role of novel gene-expression factors

The mechanisms that control cellular proliferation, as well as those related with programmed cell death or apoptosis, require precise regulation systems to prevent diseases such as cancer. Events related to cellular proliferation as well as those associated with apoptosis involve the regulation of gene expression carried out by three basic genetic expression regulation mechanisms: transcription, splicing of the primary transcript for mature mRNA formation, and RNA translation, a ribosomal machinery-dependent process for protein synthesis. While development of each one of these processes requires energy for recognition and assembly of a number of molecular complexes, it has been reported that an increased expression of several members of these protein complexes promotes apoptosis in distinct cell types. The question of how these factors interact with other proteins in order to incorporate themselves into the different transduction cascades and stimulate the development of programmed cell death, although nowadays actively studied, is still waiting for a clear-cut answer. This review focuses on the interactions established between different families of transcription, elongation, translation and splicing factors associated to the progression of apoptosis (AU)