RESUMEN
Acupuncture, taking the advantage of modality-specific neural pathways, has shown promising results in the treatment of brain disorders that affect different modalities such as pain and vision. However, the precise underlying mechanisms of within-modality neuromodulation of acupoints on human high-order cognition remain largely unknown. In the present study, we used a non-invasive and easy-operating method, focused ultrasound, to stimulate two language-relevant acupoints, namely GB39 (Xuanzhong) and SJ8 (Sanyangluo), of thirty healthy adults. The effect of focused ultrasound stimulation (FUS) on brain activation was examined by functional magnetic resonance imaging (fMRI). We found that stimulating GB39 and SJ8 by FUS evoked overlapping but distinct brain activation patterns. Our findings provide a major step toward within-modality (in this case, language) acupoint-brain (acubrain) mapping and shed light on to the potential use of FUS as a personalized treatment option for brain disorders that affect high-level cognitive functions.
Asunto(s)
Puntos de Acupuntura , Lenguaje , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Coronavirus disease-2019 (COVID-19) has become a major global epidemic. Facilitated by HTS2 technology, we evaluated the effects of 578 herbs and all 338 reported anti-COVID-19 TCM formulae on cytokine storm-related signaling pathways, and identified the key targets of the relevant pathways and potential active ingredients in these herbs. This large-scale transcriptional study innovatively combines HTS2 technology with bioinformatics methods and computer-aided drug design. For the first time, it systematically explores the molecular mechanism of TCM in regulating the COVID-19-related cytokine storm, providing an important scientific basis for elucidating the mechanism of action of TCM in treating COVID-19.
RESUMEN
Accumulation of mutant proteins is a major cause of many diseases (collectively called proteopathies), and lowering the level of these proteins can be useful for treatment of these diseases. We hypothesized that compounds that interact with both the autophagosome protein microtubule-associated protein 1A/1B light chain 3 (LC3)1 and the disease-causing protein may target the latter for autophagic clearance. Mutant huntingtin protein (mHTT) contains an expanded polyglutamine (polyQ) tract and causes Huntington's disease, an incurable neurodegenerative disorder2. Here, using small-molecule-microarray-based screening, we identified four compounds that interact with both LC3 and mHTT, but not with the wild-type HTT protein. Some of these compounds targeted mHTT to autophagosomes, reduced mHTT levels in an allele-selective manner, and rescued disease-relevant phenotypes in cells and in vivo in fly and mouse models of Huntington's disease. We further show that these compounds interact with the expanded polyQ stretch and could lower the level of mutant ataxin-3 (ATXN3), another disease-causing protein with an expanded polyQ tract3. This study presents candidate compounds for lowering mHTT and potentially other disease-causing proteins with polyQ expansions, demonstrating the concept of lowering levels of disease-causing proteins using autophagosome-tethering compounds.
Asunto(s)
Alelos , Evaluación Preclínica de Medicamentos/métodos , Proteína Huntingtina/antagonistas & inhibidores , Proteína Huntingtina/genética , Proteínas Mutantes/antagonistas & inhibidores , Proteínas Mutantes/genética , Mutación/genética , Animales , Ataxina-3/genética , Autofagosomas/metabolismo , Autofagia , Modelos Animales de Enfermedad , Proteínas de Drosophila/antagonistas & inhibidores , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Femenino , Humanos , Proteína Huntingtina/química , Proteína Huntingtina/metabolismo , Masculino , Ratones , Proteínas Asociadas a Microtúbulos/genética , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Mutación/efectos de los fármacos , Neuronas/citología , Péptidos/genética , Fenotipo , Reproducibilidad de los ResultadosRESUMEN
Rhizoma Coptidis is a widely cultivated traditional Chinese herb. Although the chemical profiles of Rhizoma Coptidis have been established previously, the biological profiling of Rhizoma Coptidis has not been conducted yet. In this study, we collected Rhizoma Coptidis varieties from four distinct growing regions and performed genome-wide biological response fingerprinting (BioReF) on HepG2 cells using a gene expression array. Similar biological pathways were affected by extracts of all four Rhizoma Coptidis varieties but not by their analogue, Mahoniae Caulis. Among these pathways, the terpenoid backbone biosynthesis pathway was highly enriched, and six genes in the mevalonate (MVA) pathway were all down-regulated. However, the expression, maturation, as well as the specific DNA binding capacity of their coordinate transcription factor, sterol response element binding protein 2 (SREBP2), was not affected by Rhizoma Coptidis extract (RCE) or its typical active alkaloid berberine. Cellular cholesterol content tests further verified the cholesterol-lowering function of RCE in vitro, which supplements evidence for the use of Rhizoma Coptidis in hyperlipidemia treatment. This is the first described example of evaluating the quality of Rhizoma Coptidis with BioReF and a good demonstration of using BioReF to uncover the mechanisms of herbs at a systematic level.