ABSTRACT
Chronic stress-induced epinephrine (EPI) accelerates breast cancer progression and metastasis, but the molecular mechanisms remain unclear. Herein, we found a strong positive correlation between circulating EPI levels and the tumoral expression of ubiquitin-specific peptidase 22 (USP22) in patients with breast cancer. USP22 facilitated EPI-induced breast cancer progression and metastasis by enhancing adipose triglyceride lipase (ATGL)-mediated lipolysis. Targeted USP22 deletion decreased ATGL expression and lipolysis, subsequently inhibiting EPI-mediated breast cancer lung metastasis. USP22 acts as a bona fide deubiquitinase for the Atgl gene transcription factor FOXO1, and EPI architects a lipolysis signaling pathway to stabilize USP22 through AKT-mediated phosphorylation. Notably, USP22 phosphorylation levels are positively associated with EPI and with downstream pathways involving both FOXO1 and ATGL in breast cancers. Pharmacological USP22 inhibition synergized with ß-blockers in treating preclinical xenograft breast cancer models. This study reveals a molecular pathway behind EPI's tumor-promoting effects and provides a strong rationale for combining USP22 inhibition with ß-blockers to treat aggressive breast cancer.
Subject(s)
Breast Neoplasms , Epinephrine , Lipolysis , Ubiquitin Thiolesterase , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Lipolysis/drug effects , Female , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , Epinephrine/metabolism , Humans , Animals , Mice , Cell Line, Tumor , Forkhead Box Protein O1/metabolism , Forkhead Box Protein O1/genetics , Lipase/metabolism , Lipase/genetics , Signal Transduction/drug effects , Neoplasm Metastasis , Phosphorylation , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Gene Expression Regulation, Neoplastic/drug effects , AcyltransferasesABSTRACT
Contralaterally controlled functional electrical stimulation (CCFES) is a rehabilitation method whose efficacy has been proved in several randomized controlled trials. Symmetrical CCFES (S-CCFES) and asymmetrical CCFES (A-CCFES) are two basic strategies of CCFES. The cortical response can reflect the instant efficacy of CCFES. However, it is still unclear of the difference on cortical responses of these different strategies. Therefore, the aim of the study is to determine what cortical response CCFES may engage. Thirteen stroke survivors were recruited to complete three training sessions with S-CCFES, A-CCFES and unilateral functional electrical stimulation (U-FES), in which the affected arm was stimulated. The electroencephalogram (EEG) signals were recorded during the experiment. The event-related desynchronization (ERD) value of stimulation-induced EEG and phase synchronization index (PSI) for resting EEG were calculated and compared in different tasks. We found that S-CCFES induced significantly stronger ERD at affected MAI(motor area of interest) in alpha-rhythm (8-15Hz), which indicated stronger cortical activity. Meanwhile, S-CCFES also increased intensity of cortical synchronization within the affected hemisphere and between hemispheres, and the significantly increased PSI occurred in a wider area after S-CCFES. Our results suggested that S-CCFES could enhance cortical activity during stimulation and cortical synchronization after stimulation in stroke survivors. S-CCFES seems to have better prospects for stroke recovery.
Subject(s)
Electric Stimulation Therapy , Stroke Rehabilitation , Stroke , Humans , Stroke Rehabilitation/methods , Electric Stimulation Therapy/methods , Electric Stimulation/methods , Electroencephalography , Cortical SynchronizationABSTRACT
Autism spectrum disorder (ASD) is a devastating mental disorder in children. Currently, there is no effective treatment for ASD. Transcranial direct current stimulation (tDCS), which is a non-invasive brain stimulation neuromodulation technology, is a promising method for the treatment of ASD. However, the manner in which tDCS changes the electrophysiological process in the brain is still unclear. In this study, we used tDCS to stimulate the dorsolateral prefrontal cortex area of children with ASD (one group received anode tDCS, and the other received sham tDCS) and investigated the changes in evoked EEG signals and behavioral abilities before and after anode and sham stimulations. In addition to tDCS, all patients received conventional rehabilitation treatment. Results show that although conventional treatment can effectively improve the behavioral ability of children with ASD, the use of anode tDCS with conventional rehabilitation can boost this improvement, thus leading to increased treatment efficacy. By analyzing the electroencephalography pre- and post-treatment, we noticed a decrease in the mismatch negativity (MMN) latency and an increase in the MMN amplitude in both groups, these features are considered similar to MMN features from healthy children. However, no statistical difference between the two groups was observed after 4 weeks of treatment. In addition, the MMN features correlate well with the aberrant behavior checklist (ABC) scale, particularly the amplitude of MMN, thus suggesting the feasibility of using MMN features to assess the behavioral ability of children with ASD.
ABSTRACT
Polyoxometalate nanoparticles were synthesized via a concise solid-state reaction method by directly grinding silver nitrate and the polyoxometalate (NH4)5H6PMo4V8O40 at room temperature without the assistance of a surfactant. The as-prepared Ag6(NH4)5PMo4V8O40 (AgPMo4V8) comprised uniform nanoparticles of 50 nm size, which provided significant catalytic oxidative desulfurization (CODS) performance using O2, N2 + O2 or air as an oxidant. The high efficiency of 100% removal was obtained using AgPMo4V8 nanoparticles as a catalyst in treating model refractory sulfurs. The coexistence of Ag+ and PMo4V8O4011- was the main contribution for this CODS procedure, and the Ag+ species was employed as the electron transfer mediator (ETM) and the PMo4V8O4011- anion was used as the electron donor. The internal electron transfer between Ag+/Ag0 and V5+/V4+ allowed AgPMo4V8 to mimic oxygenase to release the activation energy of oxygen. AgPMo4V8 nanoparticles also exhibited potential for practical catalytic application in the CODS of diesel and gasoline to produce ultra-clean oils with a S content lower than 10 ppm under mild reaction conditions using a mixture of N2 and O2, thus favoring industrial application.
ABSTRACT
We investigated changes in the anticipatory activity of the leg and trunk muscles in preparation for a step during support surface perturbation. Eight healthy subjects performed stepping tasks under three conditions: normal, forward perturbation, and backward perturbation. R and C indices were calculated for the reciprocal and co-activation patterns of muscle pairs within the time intervals typical of anticipatory postural adjustments. When the support surface perturbation occurred, anticipatory muscle activations were predominantly in the C indices in the leg muscles. Significant differences in the maximum displacement of the centre of pressure were seen between conditions (FS vs NS; BS vs FS). The results suggest that activation of the leg muscles rather than the trunk muscles was modified to ensure equilibrium for taking a step in response to support surface perturbation.