[Abundance and Fluorescent Components of Dissolved Organic Matter Affected by Land Use in a Drinking Water Source].

Regional concentrations, fluorescent components, and sources of dissolved organic matter (DOM) in a drinking water source in Chaobai River across seasons were investigated here using fluorescence excitation-emission matrices, parallel factor analysis, and fluorescence indexes. Five fluorescent-DOM components were identified, including two microbial humic-like components and one autochthonous tyrosine-like, one reduced quinone-like, and one terrestrial humic-like component. DOM was mainly derived from microorganisms. The farmland-dominated region showed the highest DOM concentration and significantly lower maximum fluorescence intensities (Fmax) of almost all fluorescent components than those in the forest-dominated region. The region dominated by urban lands exhibited obviously lower DOM concentrations than those in the farmland-dominated region and lower Fmax values of fluorescent components than those in the forest-dominated region. No interaction was found between land use and season when considering their effects on DOM. Season had a significant influence on the humification degree of DOM. This study shows that agricultural land use had a greater impact on DOM than that of forests and urban areas, and the increased riverine DOM resulting from farmland was mainly non-fluorescent parts.

Repetitive transcranial magnetic stimulation (rTMS) fails to improve cognition in patients with parkinson's disease: a Meta-analysis of randomized controlled trials.

BACKGROUND: Cognitive decline is one of the greatest concerns for patients with Parkinson's disease (PD) and their care partners. Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological treatment option used to improve cognitive function in PD, but its efficacy is unclear. We performed a meta-analysis to determine whether rTMS improves cognition in PD patients. METHODS: Eligibility criteria (PICOS) were as follows: (1) 'P': The patients participating were diagnosed with idiopathic PD; (2) 'I': Intervention using rTMS; (3) 'C': Sham stimulation as control; (4) 'O': The outcome of the study included cognitive evaluations; (5) 'S': The study adopted randomized controlled design. The standardized mean difference (SMD) of change of score was applied to measure efficacy, and we used Version 2 of the Cochrane tool to assess risk of bias. RESULTS: Twelve studies met the inclusion criteria. Compared with sham-controlled group, the pooled result showed a non-significant short-term effect of rTMS on global cognition (SMD: -0.15, 95% CI: -0.59 to 0.29, I2 = 36.7%), executive function (SMD: 0.03, 95% CI: -0.21 to 0.26, I2 = 0.0%), and attention and working memory (SMD: 0.05, 95% CI: -0.25 to 0.35, I2 = 0.0%). Long-term outcomes were either shown to be statistically nonsignificant. CONCLUSIONS: Based on a limited number of studies, rTMS fails to improve cognition in PD. We call for additional high-quality randomized controlled trials with adequate sample sizes to determine the efficacy of rTMS.

Idebenone-Activating Autophagic Degradation of α-Synuclein via Inhibition of AKT-mTOR Pathway in a SH-SY5Y-A53T Model of Parkinson's Disease: A Network Pharmacological Approach.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, which currently lacks disease-modifying therapy to slow down its progression. Idebenone, a coenzyme Q10 (CQ10) analogue, is a well-known antioxidant and has been used to treat neurological disorders. However, the mechanism of Idebenone on PD has not been fully elucidated. This study aims to predict the potential targets of Idebenone and explore its therapeutic mechanism against PD. METHOD: We obtained potential therapeutic targets through database prediction, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Next, we constructed and analyzed a protein-protein interaction network (PPI) and a drug-target-pathway-disease network. A molecular docking test was conducted to identify the interactions between Idebenone and potential targets. Lastly, a PD cell line of SH-SY5Y overexpressing mutant α-synuclein was used to validate the molecular mechanism. RESULT: A total of 87 targets were identified based on network pharmacology. The enrichment analysis highlighted manipulation of MAP kinase activity and the PI3K-AKT signaling pathway as potential pharmacological targets for Idebenone against PD. Additionally, molecular docking showed that AKT and MAPK could bind tightly with Idebenone. In the cell model of PD, Idebenone activated autophagy and promoted α-synuclein degradation by suppressing the AKT/mTOR pathway. Pretreating cells with chloroquine (CQ) to block autophagic flux could diminish the pharmacological effect of Idebenone to clear α-synuclein. CONCLUSION: This study demonstrated that Idebenone exerts its anti-PD effects by enhancing autophagy and clearance of α-synuclein, thus providing a theoretical and experimental basis for Idebenone therapy against PD.

Alterations in intrinsic functional networks in Parkinson's disease patients with depression: A resting-state functional magnetic resonance imaging study.

AIMS: The aim of this research was to investigate the alterations in functional brain networks and to assess the relationship between depressive impairment and topological network changes in Parkinson's disease (PD) patients with depression (DPD). METHODS: Twenty-two DPD patients, 23 PD patients without depression (NDPD), and 25 matched healthy controls (HCs) were enrolled. All participants were examined by resting-state functional magnetic resonance imaging scans. Graph theoretical analysis and network-based statistic methods were used to analyze brain network topological properties and abnormal subnetworks, respectively. RESULTS: The DPD group showed significantly decreased local efficiency compared with the HC group (P = .008, FDR corrected). In nodal metrics analyses, the degree of the right inferior occipital gyrus (P = .0001, FDR corrected) was positively correlated with the Hamilton Depression Rating Scale scores in the DPD group. Meanwhile, the temporal visual cortex, including the bilateral middle temporal gyri and right inferior temporal gyrus in the HC and NDPD groups and the left posterior cingulate gyrus in the NDPD group, was defined as hub region, but not in the DPD group. Compared with the HC group, the DPD group had extensive weakening of connections between the temporal-occipital visual cortex and the prefrontal-limbic network. CONCLUSIONS: These results suggest that PD depression is associated with disruptions in the topological organization of functional brain networks, mainly involved the temporal-occipital visual cortex and the posterior cingulate gyrus and may advance our current understanding of the pathophysiological mechanisms underlying DPD.

Clinical outcomes and predictive model of platelet reactivity to clopidogrel after acute ischemic vascular events.

BACKGROUND: High on-treatment platelet reactivity (HTPR) has been suggested as a risk factor for patients with ischemic vascular disease. We explored a predictive model of platelet reactivity to clopidogrel and the relationship with clinical outcomes. METHODS: A total of 441 patients were included. Platelet reactivity was measured by light transmittance aggregometry after receiving dual antiplatelet therapy. HTPR was defined by the consensus cutoff of maximal platelet aggregation >46% by light transmittance aggregometry. CYP2C19 loss-of-function polymorphisms were identified by DNA microarray analysis. The data were compared by binary logistic regression to find the risk factors. The primary endpoint was major adverse clinical events (MACEs), and patients were followed for a median time of 29 months. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the patients with HTPR and non-HTPR. RESULTS: The rate of HTPR was 17.2%. Logistic regression identified the following predictors of HTPR: age, therapy regimen, body mass index, diabetes history, CYP2C192, or CYP2C193 variant. The area under the curve of receiver operating characteristic for the HTPR predictive model was 0.793 (95% confidence interval: 0.738-0.848). Kaplan-Meier analysis showed that patients with HTPR had a higher incidence of MACE than those with non-HTPR (21.1% vs. 9.9%; χ = 7.572, P = 0.010). CONCLUSIONS: Our results suggest that advanced age, higher body mass index, treatment with regular dual antiplatelet therapy, diabetes, and CYP2C192 or CYP2C193 carriers are significantly associated with HTPR to clopidogrel. The predictive model of HTPR has useful discrimination and good calibration and may predict long-term MACE.

RIT2 polymorphism is associated with Parkinson's disease in a Han Chinese population.

Recently, a meta-analysis including 5 large genome-wide association studies has identified rs12456492 variant of RIT2 gene as a novel risk locus for Parkinson's disease (PD) in Caucasian populations. However, the association between RIT2 polymorphism and PD risk has not been positively replicated in Asian population yet. We detected the genotypes of rs12456492 in 524 PD patients and 521 control subjects from a Han Chinese population. The allele and genotype distribution of rs12456492 variant were significantly different between PD patients and controls (allele p = 0.001, genotype p = 0.002). Logistic regression analysis showed that the G-carrying genotype (AG + GG) individuals exhibited a nearly 1.4-fold increased risk for PD compared with the AA genotype carriers (OR = 1.390; 95% confidence interval = 1.079-1.791; p = 0.011). Our data support that the carriage of G allele of rs12456492 variant of RIT2 gene significantly increases the risk for PD in Han Chinese population, suggesting a potential role of RIT2 in the etiology of PD.

The putaminal abnormalities on 3.0T magnetic resonance imaging: can they separate parkinsonism-predominant multiple system atrophy from Parkinson's disease?

BACKGROUND: The putaminal abnormalities detected on 1.5 T magnetic resonance imaging (MRI), such as putaminal atrophy, slit-like hyperintense rim, and hypointensity in the putamen on T2-weighted (T2W) imaging are important signs on differentiating multiple system atrophy with parkinsonism (MSA-P) from Parkinson's disease (PD). However, the putaminal abnormalities may have different manifestations on 3.0 T from those on 1.5 T. PURPOSE: To investigate the diagnostic value of putaminal abnormalities on 3.0 T MRI for differentiating MSA-P from PD. MATERIAL AND METHODS: The study included a MSA-P group (9 men, 9 women), a PD group (12 men, 14 women), and a control group (11 men, 13 women). All subjects were examined with 3.0 T MRI using the conventional protocol. Putaminal atrophy, T2-hypointensity in the dorsolateral putamenat, and a slit-like hyperintense rim on the lateral putamen were evaluated in each subject. RESULTS: There were no significant differences in the slit-like hyperintense rim (P = 0.782) or T2-hypointensity in the dorsolateral putamen (P = 0.338) among the three groups. Bilateral putaminal atrophy was found in 44.4% (8 of 18) of the MSA-P patients, in only 7.7% (2 of 26) of the PD patients, and in none of the controls. The proportion of subjects with putaminal atrophy was significantly higher in the MAS-P group (P = 0.008) and control group (P < 0.001). The specificity and sensitivity of putaminal atrophy for distinguishing MSA-P from PD was 92.3% and 44.4%, respectively. CONCLUSION: The signal changes in the putamen on T2W imaging on 3.0 T MRI, including slit-like hyperintense rim and putaminal hypointensity, are not specific signs for MSA-P. Putaminal atrophy is highly specific for differentiating MSA-P from PD and healthy controls, but its insufficient sensitivity limits its diagnostic value.

Triggering receptor expressed on myeloid cells 2 variants are rare in Parkinson's disease in a Han Chinese cohort.

Recent studies have reported that a rare nonsynonymous variant rs75932628-T in the TREM2 gene is associated with increased risk of Alzheimer's disease and Parkinson's disease (PD) in European-descended populations. However, the association between rare TREM2 mutations and PD risk remains unknown in Chinese population. We directly sequenced exon2 of TREM2 in a cohort of 476 PD patients and 432 healthy controls from a Han Chinese population. Rs75932628-T (p.R47H) was found in 0.2% of PD cases (1/476) but in none of the controls (0/432, p = 1.000), with a minor allele frequency of 0.06% among the 908 subjects. Our findings suggest that variants in exon2 of TREM2 are extremely rare, and it is not a genetic risk factor for PD in the southern Han Chinese population.

Mutation analysis of Parkin, PINK1, DJ-1 and ATP13A2 genes in Chinese patients with autosomal recessive early-onset Parkinsonism.

Autosomal recessive early-onset Parkinsonism (AREP) has been associated with mutations in the Parkin, PINK1, DJ-1, and ATP13A2 genes. We studied the prevalence of mutations in all four genes in 29 Chinese unrelated families with AREP using direct sequencing analysis and real-time quantitative PCR analysis assay. There are 14 families (48.3%) with mutations of Parkin gene, 2 families (6.9%) with mutations of PINK1 gene, and 1 family (3.4%) with mutation of DJ-1 gene. No pathogenic mutations in ATP13A2 gene were found in these families. Three Parkin gene mutations (c.G859T, c.1069-1074delGTGTCC, and c.T1422C) and one DJ-1 gene mutation (c.T29C) have not been reported previously. In conclusion, Parkin gene mutation is the most common pathogenic factor in Chinese patients with AREP. Mutations of DJ-1 and PINK1 gene are also found in Chinese families with AREP. Mutations in ATP13A2 gene may be rare in Chinese families with AREP.

Tenacigenin B derivatives reverse P-glycoprotein-mediated multidrug resistance inHepG2/Dox cells.

Tenacissimoside A (1) and 11alpha-O-benzoyl-12beta- O-acetyltenacigenin B (2), two derivatives of tenacigenin B (3) from the plant Marsdenia tenacissima, reversed multidrug resistance in P-glycoprotein (Pgp)-overexpressing multidrug-resistant cancer cells. The sensitivity of HepG2/Dox cells to the antitumor drugs doxorubicin, vinblastine, puromycin, and paclitexel was increased by 18-, 10-, 11-, and 6-fold by 20 microg/mL (or 25 microM) of 1 and 16-, 53-, 16-, and 326-fold by 20 microg/mL (or 39 microM) of 2, respectively. A preliminary mechanistic study has suggested that 1 might modulate Pgp-mediated multidrug resistance through directly interacting with the Pgp substrate site.

[Mutation detection of parkin gene by denaturing high performance liquid chromatography].

OBJECTIVE: To detect parkin gene mutation of early-onset parkinsonism (EOP) by denaturing high performance liquid chromatography (DHPLC). METHODS: The blood cell genomic DNA of 82 EOP patients was isolated. Exons of parkin gene were amplified by PCR. The PCR products were detected by DHPLC. The sample with abnormal peak shape was sequenced. RESULTS: Three point mutations were identified in 82 EOP patients compared with 100 healthy controls. Mutations in intron include IVS1-39 G --> T and IVS9 +18 C --> T. The T1422C mutation was in coding region and resulted in 441 Cys --> Arg. CONCLUSION: Three heterozygous mutations are found in sporadic EOP patients and genetic diagnosis of parkin gene by DHPLC is applicable in EOP patients.

[Phytochemical investigation on Lysimachia fortunei].

OBJECTIVE: To investigate the chemical constituents in the ethyl acerate extract of Lysimachia fortunei. METHOD: The compounds were isolated by silica gel chromatography, and their structures were elucidated by NMR data and references. RESULT: Nine natural constituents were isolated, and their structures were identified as 9, 19-cyclolanost-24-en-3-one (1), 24-ethyl-5alpha-cholesta-7, 22(E)-dien-3-one (2), 1-pentatriacontanol (3), beta-stigmasterol (4), 24-ethyl-5alpha-cholesta-7, 22(E)-dien-3beta-ol (5), palmitic acid (6), isorhamnetin (7), kaempferol (8) and quercetin (9) respectively. CONCLUSION: All compounds mentioned above were isolated from this plant for the first time, and compound 1, 2 and 5 were obtained from the genus for the first time.

[Mutation analysis of GCH1 gene in Chinese patients with dopa responsive dystonia].

OBJECTIVE: To detect mutations of guanosine triphosphate cyclohydrolase I (GCH1) gene in Chinese patients with dopa responsive dystonia (DRD). METHODS: Six sporadic patients with DRD were examined. GCH1 gene mutations were detected using polymerase chain reaction (PCR), DNA sequence analysis and restriction enzyme digestion analysis. One hundred normal people were detected using PCR and restriction enzyme digestion analysis. RESULTS: A new point mutation, 151(G-->A) in exon one was found in a patient. It lead to substitution of a methionine for isoleucine at amino acid 1(M1I). This mutation was not found in normal control people. CONCLUSION: The authors report a new heterozygotic point mutation 151(G-->A) in GCH1 gene. There are GCH1 gene mutations in Chinese sporadic patients with DRD.

[Exon rearrangement analysis of parkin gene in patients with isolated early-onset parkinsonism using semi-quantitative PCR].

OBJECTIVE: To investigate the value of fluorescence semi-quantitative PCR in analysis of the exon rearrangement of parkin gene in Chinese patients with isolated early-onset parkinsonism (EOP). METHODS: fluorescence semi-quantitative PCR was used to analyze the exon rearrangements of parkin gene in 61 isolated patients with EOP. RESULTS: Exon deletions in parkin gene were found in 4 of the 61 isolated patients with EOP. One of them failed to show the PCR product of exon 4 and had homozygous deletions of exon 4. The normalized ratios (NRs) of exon 2, exon 3, and exon 4 of the other 3 patients were 0.47, 0.52, and 0.49 respectively, showing that they had heterozygous deletions of exon 2, 3, and 4 respectively. No exon multiplication was found in this study. CONCLUSION: Exon rearrangement of parkin gene exists in Chinese patients with isolated EOP.

[The wild-type alpha-synuclein over-expression to induce the protein aberrant aggregation of alpha-synuclein in HEK293 cells in vitro].

OBJECTIVE: To investigate over-expression of wild-type alpha-synuclein inducing the aberrant aggregation of alpha-synuclein in HEK293 cell in vitro. METHODS: The cDNA encoding the human alpha-synuclein without the stop code was cloned into PGEM T-easy vector. Using enzyme map and DNA sequencing analyzed and determined the recombinant plasmid, and then sub-clone the alpha-synuclein cDNA fragment into pEGFP-N1 vector. The recombinant plasmids alpha-synuclein-pEGFP were transfected into HEK293 cells by lipofectamin 2000. The aberrant aggregation of alpha-synuclein was measured by EGFP fluorescence, anti-alpha-synuclein immunocytochemistry. The inclusions in the cultured cells were identified with HE staining. RESULTS: The restriction enzyme map suggested that eukaryotic expression vector for human wild-type alpha-synuclein gene was constructed successfully. By EGFP fluorescence, anti-alpha-synuclein immunocytochemistry, it could be observed that the alpha-synuclein protein could aggregate in cytoplasm and the Lewy body-like inclusions found in cytoplasm of cultured cells. CONCLUSION: The over-expression of wild-type alpha-synuclein can induce protein aberrant aggregation and Lewy body-like inclusions formation in cytoplasm of HEK293 cell in vitro.

[Genotype and phenotype analyses of three families with autosomal recessive juvenile parkinsonism].

OBJECTIVE: To investigate the gene mutations and the clinical features of Chinese patients with autosomal recessive juvenile parkinsonism(AR-JP). METHODS: the polymerase chain reaction (PCR), DNA sequence analysis, and restriction enzyme digestion analysis were applied to check parkin gene mutations of 15 index patients from 15 families with AR-JP. RESULTS: Three families were detected to have parkin mutations. Two of them had heterozygous deletion mutations (202-203 del AG in exon 2, 1069-1074 del GTGTCC in exon 9) and another of them carried a heterozygous missense mutation [1422(T-->C) in exon 12]. Two of the mutations [1069-1074delGTGTCC and 1422(T-->C)] were not reported previously. There were six patients in the three families. Mean age at onset was 25.2+/-5.7 years, ranging from 18 to 31 years. The symptoms were under slow progression, diurnal fluctuation with sleep benefit, and hyperreflexia were relatively prominent. Response to levodopa was satisfactory. CONCLUSION: There are parkin mutations happened in Chinese patients with AR-JP. Patients with parkin mutations have distinct clinical features besides the common clinical features of Parkinson's disease.

[Mutation analysis of DJ1 gene in patients with autosomal recessive early-onset Parkinsonism].

OBJECTIVE: To investigate the mutation characteristics of DJ1 gene in Chinese patients with autosomal recessive early-onset Parkinsonism (AR-EP). METHODS: Mutations of DJ1 gene were screened by polymerase chain reaction combined with DNA direct sequencing in index patients with AR-EP from 11 unrelated families. RESULTS: No pathogenetic mutations in the DJ1 gene were detected in this group. Six intronic DJ1 polymorphisms (IVS1-15T-->C, IVS4+30T-->G, IVS4+45G-->A, IVS4+46G-->A, IVS5+31G-->A, g.168-185del) were found. Three of them (IVS1-15T-->C, IVS4+45G-->A, IVS4+46G-->A) were not reported previously. CONCLUSION: DJ1 mutations were rare in Chinese patients with autosomal recessive early-onset Parkinsonism.