An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
Our previous study has demonstrated that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A_(1))can prevent acrylamide(ACR)-induced cytotoxicity in small intestine cells.However,the potential mechanism re...Our previous study has demonstrated that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A_(1))can prevent acrylamide(ACR)-induced cytotoxicity in small intestine cells.However,the potential mechanism remains poorly understood.In this study,ACR treatment was found to increase the levels of 8-hydroxy deoxyguanine(8-OHdG)and phosphorated histone H_(2)AX(γH_(2)AX),two DNA damage markers,thereby resulting in cell cycle arrest in the G2/M phase;whereas both A_(1) and D-A_(1) could prevent the phosphorylation of ataxia telangiectasia mutated(ATM)and checkpoint kinase 2(Chk2),and then regulate the expression of G2/M phase-related proteins,finally maintaining normal cell cycle progression.Moreover,A_(1) and D-A_(1) could increase the B cell lymphoma 2(Bcl-2)/Bcl2-associated X(Bax)ratio and decrease the expression of cleaved caspase-3 and cleaved caspase-9 proteins to alleviate ACR-induced cell apoptosis,which might be related to the inhibition of the mitogen-activated protein kinase(MAPK)pathway.More importantly,A_(1) showed no remarkable variation in inhibitory effect before and after digestion,indicating that it can endure gastrointestinal digestion and may be a promising phytochemical to alleviate ACR-induced intestinal cell damage.展开更多
In this paper we proved the A_(p)-weighted inequalities for martingale transforms and differential subordinations of Banach-space-valued regular maringales.We discussed the relations between the weighted inequalities,...In this paper we proved the A_(p)-weighted inequalities for martingale transforms and differential subordinations of Banach-space-valued regular maringales.We discussed the relations between the weighted inequalities,A_(p)-weight functions and the Banach spaces which has the UMD property or are isomorphic to Hilbert space.展开更多
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
基金supported by the project from National Natural Science Foundation of China(31671962)Excellent Youth Foundation of Education Department of Hunan Province(23B0229)Fundamental Research Funds for the Central Universities(2662019PY034).
文摘Our previous study has demonstrated that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A_(1))can prevent acrylamide(ACR)-induced cytotoxicity in small intestine cells.However,the potential mechanism remains poorly understood.In this study,ACR treatment was found to increase the levels of 8-hydroxy deoxyguanine(8-OHdG)and phosphorated histone H_(2)AX(γH_(2)AX),two DNA damage markers,thereby resulting in cell cycle arrest in the G2/M phase;whereas both A_(1) and D-A_(1) could prevent the phosphorylation of ataxia telangiectasia mutated(ATM)and checkpoint kinase 2(Chk2),and then regulate the expression of G2/M phase-related proteins,finally maintaining normal cell cycle progression.Moreover,A_(1) and D-A_(1) could increase the B cell lymphoma 2(Bcl-2)/Bcl2-associated X(Bax)ratio and decrease the expression of cleaved caspase-3 and cleaved caspase-9 proteins to alleviate ACR-induced cell apoptosis,which might be related to the inhibition of the mitogen-activated protein kinase(MAPK)pathway.More importantly,A_(1) showed no remarkable variation in inhibitory effect before and after digestion,indicating that it can endure gastrointestinal digestion and may be a promising phytochemical to alleviate ACR-induced intestinal cell damage.
文摘In this paper we proved the A_(p)-weighted inequalities for martingale transforms and differential subordinations of Banach-space-valued regular maringales.We discussed the relations between the weighted inequalities,A_(p)-weight functions and the Banach spaces which has the UMD property or are isomorphic to Hilbert space.
