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141.
Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease that affects exocrine glands. To study the molecular mechanism and identify crucial genes/pathways in pSS pathogenesis, the microarray-based whole-genome gene expression profiles from salivary glands of patients with pSS and non-sicca controls were retrieved. After normalization and subsequent batch effect adjustment, significance analysis of microarrays method was applied to five available datasets, and 379 differentially expressed genes (DEGs) were identified. The 300 upregulated DEGs were enriched in Gene Ontology terms of immune and inflammatory responses, including antigen processing and presentation, interferon-mediated signaling pathway, and chemotaxis. Previously reported pSS-associated genes, including HLA-DRA, TAP2, PRDM1, and IFI16, were found to be significantly upregulated. The downregulated DEGs were enriched in pathways of salivary secretion, carbohydrate digestion and absorption, and starch and sucrose metabolism, implying dysfunction of salivary glands during pathogenesis. Next, a protein-protein interaction network was constructed, and B2M, an upregulated DEG, was shown to be a hub, suggesting its potential involvement in pSS development. In summary, we found the activation of pSS-associated genes in pathogenesis, and provide clues for salivary glands dysfunction. Experimental investigation on the identified DEGs in this study will deepen our understanding on pSS.  相似文献   
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A series of 4-hydroxyl aurone derivatives were designed synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer’s disease. The results demonstrated that most of the derivatives exhibited good multifunctional properties. Among them, compound 14e displayed good inhibitory activities of self- and Cu2+-induced Aβ1–42 aggregation with 99.2% and 84.0% at 25 μM, respectively, and high antioxidant activity with a value 1.90-fold of Trolox. In addition, 14e also showed remarkable inhibitory activities of both monoamine oxidase A and B with IC50 values of 0.271 μM and 0.393 μM, respectively. However the 6-methoxyl aurones 15ac revealed excellent selectivity toward MAO-B. Furthermore, the representative compounds 14e and 15b displayed good metal-chelating abilities and blood–brain barrier (BBB) permeabilities in vitro.  相似文献   
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帕金森病是人类第二大神经退行性疾病,虽然通过对帕金森病遗传家族的研究已发现不少与之相关的致病基因,然而其病因尚不清楚。在已发现的与帕金森病相关基因中,α-synuclein、LRRK2、Parkin、PINK1以及DJ-1也在调节神经元突触前囊泡的神经递质释放以及突触前囊泡循环过程中发挥重要作用。最近的一些研究表明突触前囊泡循环障碍在帕金森病发病过程中扮演重要角色。本文对上述基因在突触囊泡循环以及其突变导致帕金森病病程中的作用作一概述,并推测囊泡循环障碍在帕金森病发病过程中的作用机理,最后指出目前在该研究领域需要解决的一些问题。  相似文献   
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This study focused on culture-dependent survey of important bacterial community diversity of hot springs of Odisha. India. Molecular and cultural techniques were employed for assessing and exploiting the genetic and functional variability among the isolates obtained from three alkaline and mesophilic hot springs. A total of 48 isolates belonging to family Bacillaceae, Paenibacillaceae, Planococcaceae, Pseudomonadaceae and Enterobacteriaceae were identified. Majority of the bacterial isolates were affiliated with the genus Bacillus. Morphologically all the isolated bacteria were either Gram-positive spore-forming rods, or Gram-negative rods. The optimum temperature for growth of the isolates varied between 37°C to 50°C. The functional diversity revealed that many of the predominant and scarce isolates produced a variety of extracellular enzymes such as amylase, cellulase, lipase, phosphatase and protease, and genus Bacillus dominated for extracellular enzymatic activity. We employed two molecular markers to characterize the isolates. The hsp60 universal target sequence was found to be more discriminatory than 16s rRNA gene sequences. The cultivable bacterial community structure that colonized in the investigated thermal springs did not reveal much overlapping. Our results indicate that bacteria in the geothermal environment are metabolically active and cultivable populations may have great potential in biotechnology.  相似文献   
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