Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Nurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson's disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.</p><p><b>METHODS</b>The mRNA levels of Nurr1 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 Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.</p><p><b>RESULTS</b>The relative Nurr1 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 Nurr1 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 Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001).</p><p><b>CONCLUSIONS</b>DA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.</p>

Association of serum uric acid levels with the progression of Parkinson's disease in Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Uric acid (UA) is suspected to play a neuro-protective role in Parkinson's disease (PD). This study aimed to evaluate whether the serum UA level was associated with the disease progression of PD in a relatively large population of Chinese patients.</p><p><b>METHODS</b>Serum UA levels were measured from 411 Chinese PD patients and 396 age-matched controls; following the uric acid colorimetric method, the serum creatinine (Scr) levels were also measured to reduce the bias caused by possible differences in renal excretion function. The disease progression was scored by Hoehn and Yahr (H&Y) scales and disease durations; PD group was divided into 3 subgroups according to H&Y scales. Independent-samples t test was performed to analyze the differences between PD group and control group. Multiple analysis of covariance was performed to analyze the differences between PD subgroups. Spearman rank-correlation was performed to evaluate the associations between serum UA or Scr level and disease progression.</p><p><b>RESULTS</b>PD patients were found to have significantly lower levels of serum UA than controls ((243.38 ± 78.91) vs. (282.97 ± 90.80) µmol/L, P < 0.01). As the disease progression, the serum UA levels were gradually reduced. There was a significantly inverse correlation of UA levels with H&Y scales (Rs = -0.429, P < 0.01) and disease duration (Rs = -0.284, P < 0.01) in PD patients of both females and males. No significant difference of the Scr level between PD patients and controls was found ((70.01 ± 14.70) vs. (69.84 ± 16.46) µmol/L), and the Scr level was not involved in disease progression.</p><p><b>CONCLUSION</b>Lower serum UA levels may possess a higher risk of PD, which may be a potential useful biomarker to indicate the progression of PD.</p>

A probability analysis for HLA matching in adult stem cell transplantation treating nervous genetic diseases / 中国实验血液学杂志

The aim of this study was to investigate the clinical feasibility of adult stem cell transplantation for lethal mono-gene inherited disease, Duchenne muscular dystrophy (DMD). A total of 30 blood samples from DMD patients were genotyped with HLA-A,-B and -DR alleles by means of polymerase chain reaction-reverse sequence specific oligonucleotide (PCR-RSSO). The HLA gene types in 30 DMD patients were compared with those of 668 unrelated donors from Umbilical Cord Blood Center of Guangdong Province and 34 910 unrelated donors from Chinese Bone Marrow Bank. The results showed that HLA gene of the DMD group was inherited in normal distribution. There was no striking difference of HLA-A, -B and -DR alleles expression between the DMD patients group and control healthy group. 25% of the DMD patients got suitable donors for stem cell transplantation, in which 15 patients found donors with >or= 5/6 HLA match at the Umbilical Cord Blood Center of Guangdong Province, i.e. occupying 50% of the total. Eight patients got 6/6 HLA matching donors at the Chinese Bone Marrow Bank, i.e. occupying 26% of the total. It is concluded that stem cells transplantation therapy for DMD patients is feasible, which will benefit these patients suffered from the lethal neuromuscular disease, and create a new way to treat this tough nervous system disease.

Comparison and analysis of the molecular character of breakpoints in introns of deletion hotspots of dystrophin gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the exons deletion mechanisms for dystrophin gene, the molecular characters of breakpoints of junction fragments for deletion-type Duchenne muscular dystrophy (DMD) patients with 46 and 51 exons deletion were compared and analyzed.</p><p><b>METHODS</b>Deletion-type DMD patients were detected by multiplex polymerase chain reaction(mPCR). The breakpoints of junction fragments with 46 and 51 exons deletions were cloned and sequenced respectively.</p><p><b>RESULTS</b>Analysis of sequences of deletion-junction fragment of exon 46 showed that the 5'breakpoint was located in AT-rich region of intron 45 and the 3' breakpoint was in medium reiteration repeats (MER1) sequence. There existed 2 bp(ta) junction homology between two breakages. No small insertion, small deletion or point mutation was located near the junction point. Similarly, analysis of sequences of deletion-junction fragment of exon 51 showed that the 5 breakpoint was located in transposon-like human elements (THE1) of intron 50 and the 3' breakpoint was in L2 sequence. There existed 3 bp(cta) junction homology between two breakages. No small insertion, small deletion or point mutation was located near the junction point. By analyzing the secondary structure of junction fragments with 46 and 51 exons deletions, it was demonstrated that all breakpoints of junction fragments were located at the non-matching regions of single-strand hairpin.</p><p><b>CONCLUSION</b>By comparing the junction fragments with 46 or 51 exons deletion, it was found that all of breakpoints were located in repeat sequences and the repeat sequences formed the single-strand hairpin which could make the introns instable and result in exon deletion.</p>

Minocycline protects dopaminergic neurons in lipopolysaccharide.induced model of Parkinson' s disease / 中华神经科杂志

Objective To further investigated the effect of minocycline on the inhibition of microglial activation and subsequent protection of nigral DA neuron.Methods 20 rats injected with LPS in the substantia nigra (SN) were randomly divided into two groups (LPS group and LPS+Minocycline group).The behavior was observed on the 7~(th) d and 14~(th) d.The immunohistoehemistry,in situ hybridization and Western-blot were used to detect the levels of positive neuron,mRNA,protein of TH and OX-42. Results The slightly rotational behavior was observed in LPS+Minoeyeline group.The majority of mieroglias were activated in the two groups.Some microglia in the SNpc remained ramified in LPS+ Minocycline group.The numbers of hypertophie microglia in LPS+Minoeyeline group were less than that in LPS group.Western-blot showed that the protein of OX-42 in two LPS groups was higher than in normal group(P