RESUMEN
USP7, which encodes a deubiquitylating enzyme, is among the most frequently mutated genes in pediatric T-ALL, with somatic heterozygous loss-of-function mutations (haploinsufficiency) predominantly affecting the subgroup that has aberrant TAL1 oncogene activation. Network analysis of > 200 T-ALL transcriptomes linked USP7 haploinsufficiency with decreased activities of E-proteins. E-proteins are also negatively regulated by TAL1, leading to concerted down-regulation of E-protein target genes involved in T-cell development. In T-ALL cell lines, we showed the physical interaction of USP7 with E-proteins and TAL1 by mass spectrometry and ChIP-seq. Haploinsufficient but not complete CRISPR knock-out of USP7 showed accelerated cell growth and validated transcriptional down-regulation of E-protein targets. Our study unveiled the synergistic effect of USP7 haploinsufficiency with aberrant TAL1 activation on T-ALL, implicating USP7 as a haploinsufficient tumor suppressor in T-ALL. Our findings caution against a universal oncogene designation for USP7 while emphasizing the dosage-dependent consequences of USP7 inhibitors currently under development as potential cancer therapeutics.
Asunto(s)
Oncogenes/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteína 1 de la Leucemia Linfocítica T Aguda/genética , Peptidasa Específica de Ubiquitina 7/genética , Sistemas CRISPR-Cas/genética , Línea Celular Tumoral , Linaje de la Célula/genética , Proliferación Celular/genética , Regulación Leucémica de la Expresión Génica/genética , Haploinsuficiencia/genética , Humanos , Pediatría , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Activación Transcripcional/genéticaRESUMEN
Coprinus comatus, an edible and medicinal mushroom, not only tastes delicious, but also has various pharmacological activities. Recently, it has been reported that researchers have extracted more and more active ingredients, including polysaccharides, comatin, active protein complexes, and phenols from fruit bodies, mycelium, or fermentation liquor of C. comatus and studied their corresponding functions. At present, researchers mainly focus on the hypoglycemic effect of C. comatus, while other effects are less studied. This paper summarizes not only the hypoglycemic effect of C. comatus, but also other functions, such as antioxidant activity, alcohol liver protection, cancer inhibition, antiandrogenic function, anti-inflammatory effect, treatment of leukemia, and so on, which will provide scientific basis for the deep processing and comprehensive utilization of C. comatus.
Asunto(s)
Productos Biológicos/farmacología , Coprinus/química , Animales , Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Productos Biológicos/aislamiento & purificación , Humanos , Hipoglucemiantes/farmacología , RatonesRESUMEN
As a longstanding problem, Alzheimer's disease (AD) has stymied researchers in the medical field with its increasing incidence and enormous treatment difficulty. Silymarin has always been valued by researchers for its good efficacy and safety in treating liver disease. Recent studies have shown that silymarin also has good pharmacological activity in the nervous system, especially for the treatment of AD. Silymarin can control the production of Aß by inhibiting the precursor substance of Aß (ß-amyloid precursor protein), and it can inhibit the polymerization of Aß. Silymarin can also increase the acetylcholine content in the nervous system by inhibiting cholinesterase activity. At the same time, it also has the effect of resisting oxidative stress and the inflammatory response of the nervous system. These pharmacological activities contribute to the inhibition of the onset of AD. The good efficacy of silymarin on AD and its high safety and availability give it huge potential for the treatment of AD.