Research progress on induced autophagy for the treatment of oral cancer / 口腔疾病防治

@#Oral cancer has a high degree of malignancy, easily recurs, readily metastasizes and poor progonsis. Autophagy is a catabolic process induced in cells under stressful conditions. In recent years, studies have found that the activation of autophagy in epithelial cells can inhibit carcinogenesis and activate pathways such as mTOR and MAPK to activate autophagy in oral cancer cells and inhibit their survival. Inducing autophagy can degrade eukaryotic initiation factor 4E protein and inhibit oral cancer metastasis. Inducing autophagy in oral cancer cells can inhibit their proliferation and promote their apoptosis. Adding autophagy inducers to the treatment can help improve its efficacy and patient survival compared with chemoradiotherapy alone. In addition, the induction of autophagy in oral cancer cells can improve the body's immune function and enhance the efficacy of oral cancer immunotherapy. This article summarizes the relationship between autophagy and oral cancer and the role of induced autophagy in the treatment of oral cancer with the combined application of chemoradiotherapy and immunotherapy. The goal is to provide new ideas for inducing autophagy during the treatment of oral cancer, improving the therapeutic effect of oral cancer and the survival rate of patients. At present, the mechanism of action of induced autophagy in the treatment of oral cancer is not clear. Future research should study its mechanism of action, improve its therapeutic effect on oral cancer and develop autophagy inducers to accurately regulate and induce autophagy during the treatment of oral cancer.

Pharmacological insights into autophagy modulation in autoimmune diseases

As a cellular bulk degradation and survival mechanism, autophagy is implicated in diverse biological processes. Genome-wide association studies have revealed the link between autophagy gene polymorphisms and susceptibility of autoimmune diseases including systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), indicating that autophagy dysregulation may be involved in the development of autoimmune diseases. A series of autophagy modulators have displayed protective effects on autoimmune disease models, highlighting the emerging role of autophagy modulators in treating autoimmune diseases. This review explores the roles of autophagy in the autoimmune diseases, with emphasis on four major autoimmune diseases [SLE, rheumatoid arthritis (RA), IBD, and experimental autoimmune encephalomyelitis (EAE)]. More importantly, the therapeutic potentials of small molecular autophagy modulators (including autophagy inducers and inhibitors) on autoimmune diseases are comprehensively analyzed.

Avances terapéuticos en errores innatos del metabolismo: pequeñas moléculas / Therapeutic advances in inborn errors of metabolism: small molecules

Resumen La mayoría de los Errores Innatos del Metabolismo (EIM) no tienen un tratamiento efectivo. Las terapias tradicionales tratan de reducir los sustratos, reemplazar el producto no formado, que puede ser esencial y suplementar con cofactores. También se emplea la activación de vías alternativas para la eliminación de productos intermedios tóxicos, como en el caso de los defectos del ciclo de la urea y para algunas condiciones, se dispone de la terapia de reemplazo enzimático (TRE), del trasplante de células hematopoyéticas y del trasplante hepático. En los últimos años se han desarrollado nuevas estrategias e caces para tratar estas enfermedades. Con esta revisión, se busca explicar de forma sencilla las distintas opciones terapéuticas más recientes, y en algunos casos, tratamientos prometedores para ciertos errores innatos de metabolismo (EIM). En concreto se hará referencia en primer lugar al uso terapéutico de pequeñas moléculas activas, que han surgido en las últimas dos décadas como un enfoque promisorio para el tratamiento de este heterogéneo grupo de trastornos, que incluyen terapia para restauración de la lectura, chaperonas farmacológicas, reguladores de la proteostasis, inhibidores de sustrato e inductores de autofagia. Estas pequeñas moléculas actúan en diferentes niveles celulares, y el conocimiento de los distintos procesos proporciona nuevas herramientas para establecer un tratamiento innovador.

Abstract Most Inborn Errors of Metabolism diseases do not have an effective treatment. Traditional therapies try to reduce substrates, replace non-formed product, which may be essential and supplement with cofactors. Activation of alternative routes for the disposal of toxic intermediates is also employed, as in the case of urea cycle defects for some conditions, enzyme replacement therapy (ERT), Hematopoietic Cell Transplantation and liver transplantation are available. In recent years new effective strategies have been developed to treat these diseases. This review seeks to explain in a simple way the different therapeutic options and, in some cases, promising treatments for certain inborn errors of metabolism (IEM). Specifically, reference will be made first to the therapeutic use of small active molecules, which have emerged in the last two decades as a promising approach for the treatment of this heterogeneous group of disorders, including: read-through therapy, pharmacological chaperones, protease inhibitors, substrate inhibitors and autophagy inducers. These small molecules act on different cellular levels, and the knowledge of the different processes provides new tools to establish an innovative treatment.