Dopamine Agonists Exert Nurrl-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson＇s Disease

Background： Nurrl plays an essential role in the development, survival, and function maintenance ofmidbrain dopaminergic （DA） neurons, and it is a potential target for Parkinson＇s disease （PD）. Nurrl mRNA can be detected in peripheral blood mononuclear cells （PBMCs）, but whether there is any association of altered Nurrl expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurrl mRNA level in PBMC and evaluate the effect of Nurrl expression by DA agents in vivo and in vitro. Methods： The mRNA levels of Nurrl in PBMC of four subgroups of 362 PD patients and 193 healthy controls （HCs） using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurrl expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurrl expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level. Results： The relative Nurrl mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments （de novo） （P 〈 0.001 ） and HC groups （P 〈 0.010）, respectively. Furthermore, the increase in Nurr I mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurrl mRNA expression level in PBMC. In vitlv, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurrl mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively （P 〈 0.001 ）. Conclusions： DA agonists can induce Nurrl expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.

Dopamine agonist responsive burning mouth syndrome:Report of eight cases

BACKGROUND Burning mouth syndrome(BMS)is characterized by burning sensation of the oral mucosa.There is a lack of effective treatment.In recent years,a special subtype of BMS has been reported,in which oral burning sensation is alleviated after chewing,speaking,or dopaminergic drug delivery.Currently,there are few reports about the subtype of BMS in China.This study was a retrospective analysis of the clinical data of BMS patients sensitive to dopamine agonist at our hospital,aiming to improve the recognition on this disease.CASE SUMMARY Eight patients diagnosed with dopamine agonist responsive BMS at the Liaocheng People's Hospital from January 1,2017 to June 30,2020 were recruited.The clinical manifestations,treatment,and prognosis were retrospectively analyzed.There were three male and five females in the eight patients.The median age was 56 years(range,46-65 years).All the eight patients showed burning pain in the mouth.The symptoms were mild in the morning and severe in the evening,and alleviated after chewing,talking,and other oral activities.Four patients were accompanied by restless legs syndrome(RLS).Family history of RLS was positive in two patients.All patients were treated with pramipexol,and symptoms were basically relieved after 2-8 wk.CONCLUSION Dopamine agonist responsive BMS is a special subtype of BMS,which is alleviated after oral activities.Dopamine receptor agonist is an effective treatment.

Pharmacodynamic model of dopamine D1 receptor agonists in the treatment of breast cancer lung metastasis

Previous study has shown that dopamine D1 receptor(D1DR)agonists,fenoldopam(FEN)and l-stepholidine(l-SPD),have inhibitory effects on breast cancer lung metastasis.To quantitatively describe and predict the pharmacodynamic(PD)properties of FEN and l-SPD and to explore the PD model structure of cancer metastasis treating drugs,we used the data of lung metastasis in 4T1 breast cancer mice under the treatment of either FEN or l-SPD,and established a PD model.The PD model assumed an exponential growth for both primary tumor and metastasis.The primary tumor emitted cells to form metastases,and the cell emitting rate was proportional to power form of the primary tumor weight.The total number of lung metastasis was set as the target value.D1DR agonists inhibited metastasis by inhibiting cell emitting rate instead of the growth rate of primary tumor or metastasis.The model results showed that the decrease in the number of lung metastases was roughly proportional to the square of the drug dose.The values of PD coefficient reflected the inhibitory ability of the drugs,and that of l-SPD(0.274 kg/mg)was greater than that of FEN(0.0393 kg/mg).This PD model can quantitatively describe the effects of FEN and l-SPD on the progression of lung metastasis in 4T1 primary breast cancer mice and can predict the time course of drug efficacy at multiple doses,providing a reference for PD model structure of other drugs for cancer metastasis indication.