Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Cu...Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.展开更多
Non-small cell lung cancer(NSCLC)is a highly lethal cancer,and better treatments are urgently needed.Many studies have implicated circular RNAs(circRNAs)in the progression of multiple malignant tumors.Nonetheless,the ...Non-small cell lung cancer(NSCLC)is a highly lethal cancer,and better treatments are urgently needed.Many studies have implicated circular RNAs(circRNAs)in the progression of multiple malignant tumors.Nonetheless,the functions of circRNAs in NSCLC remain unclear.To study new targets for the treatment of NSCLC,circRNA expression profiling was performed on NSCLC tissues and para-carcinoma nonmalignant tissues.RNA was isolated and used for circRNA sequencing.Biological studies were performed in vitro and in vivo to determine the functions of circRNAs in NSCLC,including their functions in cell proliferation and migration.How circRNAs function in NSCLC was explored to clarify the underlying regulatory mechanisms.We found that circUCP2 was upregulated in NSCLC tissues compared with neighboring nonmalignant tissues.circUCP2 promoted the proliferation and metastasis of NSCLC cells.circUCP2 promoted NSCLC progression by sponging miR-149 and upregulating UCP2.The circUCP2/miR-149/UCP2 axis accelerates the progression of NSCLC,and circUCP2 may therefore be a novel diagnostic biomarker for the progression of NSCLC.展开更多
基金supported by the National Natural Science Foundation of China,No.82071254(to WZ).
文摘Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.
基金supported by grants from the Science and Technology Program of Guangzhou(202102080084,Han Yang)the Key Project of Scientific Research Plan of Hunan Provincial Health Commission(C202301047982,Wei Du)+1 种基金the Wings Scientific and Technological Foundation of The First People’s Hospital of Changde City(2022ZZ05,Wei Du)the Traditional Chinese Medicine Bureau of Guangdong Province(20161062,Qing Liu).
文摘Non-small cell lung cancer(NSCLC)is a highly lethal cancer,and better treatments are urgently needed.Many studies have implicated circular RNAs(circRNAs)in the progression of multiple malignant tumors.Nonetheless,the functions of circRNAs in NSCLC remain unclear.To study new targets for the treatment of NSCLC,circRNA expression profiling was performed on NSCLC tissues and para-carcinoma nonmalignant tissues.RNA was isolated and used for circRNA sequencing.Biological studies were performed in vitro and in vivo to determine the functions of circRNAs in NSCLC,including their functions in cell proliferation and migration.How circRNAs function in NSCLC was explored to clarify the underlying regulatory mechanisms.We found that circUCP2 was upregulated in NSCLC tissues compared with neighboring nonmalignant tissues.circUCP2 promoted the proliferation and metastasis of NSCLC cells.circUCP2 promoted NSCLC progression by sponging miR-149 and upregulating UCP2.The circUCP2/miR-149/UCP2 axis accelerates the progression of NSCLC,and circUCP2 may therefore be a novel diagnostic biomarker for the progression of NSCLC.