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21.
Mehmet Ciftci 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):485-489
Inhibitory effects of some drugs on glucose 6-phosphate dehydrogenase from the erythrocytes of rainbow trout (Oncorhynchus mykiss Walbaum, 1792) were investigated. The enzyme was purified 2488-fold in a yield of 76.8% using ammonium sulfate precipitation and 2′,5′-ADP Sepharose 4B affinity gel at 4°C. The drugs pental sodium, MgSO4, vancomycin, metamizol, marcaine, and prilocaine all exhibited inhibitory effects on the enzyme. While MgSO4 (Ki = 12.119 mM), vancomycin (Ki = 1.466 mM) and metamizol (Ki = 0.392 mM) showed competitive inhibition, pental sodium (Ki = 0.748 mM) and marcaine (Ki = 0.0446 mM) displayed noncompetitive inhibition. 相似文献
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《MABS-AUSTIN》2013,5(3):620-629
We recently reported the identification of Δ42PD1, a novel alternatively spliced isoform of human PD1 that induces the production of pro-inflammatory cytokines from human peripheral blood mononuclear cells and enhances HIV-specific CD8+ T cell immunity in mice when engineered in a fusion DNA vaccine. The detailed functional study of Δ42PD1, however, has been hampered due to the lack of a specific monoclonal antibody (mAb). In this study, we generated 2 high-affinity mAbs, clones CH34 (IgG2b) and CH101 (IgG1), from Δ42PD1-immunized mice. They recognize distinct domains of Δ42PD1 as determined by a yeast surface-displaying assay and ELISA. Moreover, they recognize native Δ42PD1 specifically, but not PD1, on cell surfaces by both flow cytometry and immunohistochemical assays. Δ42PD1 appeared to be expressed constitutively on healthy human CD14+ monocytes, but its level of expression was down-regulated significantly during chronic HIV-1 infection. Since the level of Δ42PD1 expression on CD14+ monocytes was negatively correlated with the CD4 count of untreated patients in a cross-sectional study, Δ42PD1 may play a role in HIV-1 pathogenesis. Lastly, when examining Δ42PD1 expression in human esophageal squamous-cell carcinoma tissues, we found high-level expression of Δ42PD1 on a subset of tumor-infiltrating T cells. Our study, therefore, resulted in 2 Δ42PD1-specific mAbs that can be used to further investigate Δ42PD1, a novel immune regulatory protein implicated in HIV-1 and tumor pathogenesis as well as other immune diseases. 相似文献
24.
Hee Jung Koo Jee Eun Yang Jae Hyung Park Daekyun LeeSeung R. Paik 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(6):972-976
In this report, mutual effect of α-synuclein and GPX-1 is investigated to unveil their involvement in the PD pathogenesis in terms of cellular defense mechanism against oxidative stress. Biochemical and immunocytochemical studies showed that α-synuclein enhanced the GPX-1 activity with Kd of 17.3 nM and the enzyme in turn markedly enhanced in vitro fibrillation of α-synuclein. Transmission electron microscopy revealed the fibrillar meshwork of α-synuclein containing GPX-1 located in locally concentrated islets. The entrapped enzyme was demonstrated to be protected in a latent form and its activity was fully recovered as released from the matrix. Therefore, novel defensive roles of α-synuclein and its amyloid fibrils against oxidative stress are suggested as the GPX-1 stimulator and the active depot for the enzyme, respectively. 相似文献
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The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case–control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel–Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR = 1.212 for T allele, 95% CI = 1.097–1.340, p-value = 0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR = 1.187 for T allele, 95% CI = 1.058–1.332, p-value = 0.004) and Asian samples (allelic model, pooled OR = 1.293 for T allele, 95% CI = 1.058–1.580, p-value = 0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value = 0.0149) and CHB (Chinese, p-value = 0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD. 相似文献
28.
Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 1–2% of the population over the age of 65. Both genetic and environmental factors trigger risks of and protection from PD. However, the molecular mechanism of PD is far from being clear. In this study, we downloaded the gene expression profile of PD from Gene Expression Omnibus and identified differentially expressed genes (DEGs) and dysfunctional pathways in PD patients compared with controls. To further understand how these pathways act together to account for the initiation of PD, we constructed a pathway crosstalk network by calculating the Jaccard index among pathways. A total of 873 DEGs and 16 dysfunctional pathways between PD patients and controls were identified. Through constructing a network of pathways, the relationships among PD pathways were visually presented by their interactions. Our results demonstrate the existence of crosstalk between different pathways in PD pathogenesis. These results not only may explain the causes of PD, but could also open the door to new therapeutic approaches for this disease. 相似文献
29.
Previous studies on the association between glycogen synthase kinase 3 beta (GSK3-β) polymorphisms (rs334558 and rs6438552) and Parkinson's disease (PD) susceptibility remained inconsistent. Thus, the goal of this study was to re-examine their exact association by a meta-analysis. All eligible studies were identified by a systematic literature search of multiple databases. Six studies (3105 cases and 4387 controls) on rs334558 and six studies (2579 cases and 4091 controls) on rs6438552 were included. The quality of these studies was generally good according to the Newcastle–Ottawa Scale (NOS). The meta-analysis showed null association between the two variants and PD susceptibility in all genetic models from the overall or Caucasian population. However, the analysis of rs334558 revealed that the risk of PD decreased in heterozygote, dominant or additive models (OR = 0.60, 95% CI: 0.48, 0.74; OR = 0.63, 95% CI: 0.51, 0.78; OR = 0.82, 95% CI: 0.71, 0.94, respectively) from the Eastern Asian population. Moreover, the analysis on the homozygote, heterozygote, dominant or additive models suggested that rs6438552 also reduced the PD risk (OR = 0.45, 95% CI: 0.24, 0.84; OR = 0.62, 95% CI: 0.39, 0.97; OR = 0.57, 95% CI: 0.37, 0.87; OR = 0.66, 95% CI: 0.49, 0.88, respectively) in the Eastern Asian population. Together, the findings suggest that the two variants both reduced the risk of PD in the Eastern Asian subgroup but not in the overall and Caucasian populations, which should be cautiously interpreted because of limited number of included studies. 相似文献
30.
Nanomaterials with superior physiochemical properties have been rapidly developed and integrated in every aspect of cell engineering and therapy for translating their great promise to clinical success. Here we demonstrate the multifaceted roles played by innovatively-designed nanomaterials in addressing key challenges in cell engineering and therapy such as cell isolation from heterogeneous cell population, cell instruction in vitro to enable desired functionalities, and targeted cell delivery to therapeutic sites for prompting tissue repair. The emerging trends in this interdisciplinary and dynamic field are also highlighted, where the nanomaterial-engineered cells constitute the basis for establishing in vitro disease model; and nanomaterial-based in situ cell engineering are accomplished directly within the native tissue in vivo. We will witness the increasing importance of nanomaterials in revolutionizing the concept and toolset of cell engineering and therapy which will enrich our scientific understanding of diseases and ultimately fulfill the therapeutic demand in clinical medicine. 相似文献