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91.
Fong Ping Chong Khuen Yen Ng Rhun Yian Koh Soi Moi Chye 《Cellular and molecular neurobiology》2018,38(5):965-980
Alzheimer’s disease (AD) is characterized by progressive memory loss and cognitive function deficits. There are two major pathological hallmarks that contribute to the pathogenesis of AD which are the presence of extracellular amyloid plaques composed of amyloid-β (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Despite extensive research that has been done on Aβ in the last two decades, therapies targeting Aβ were not very fruitful at treating AD as the efficacy of Aβ therapies observed in animal models is not reflected in human clinical trials. Hence, tau-directed therapies have received tremendous attention as the potential treatments for AD. Tauopathies are closely correlated with dementia and immunotherapy has been effective at reducing tau pathology and improving cognitive deficits in animal models. Thus, in this review article, we discussed the pathological mechanism of tau proteins, the key factors contributing to tauopathies, and therapeutic approaches for tauopathies in AD based on the recent progress in tau-based research. 相似文献
92.
K. E. Mock J. C. Brim Box J. P. Chong J. Furnish J. K. Howard 《Molecular ecology》2013,22(24):6060-6073
We investigate population genetic structuring in Margaritifera falcata, a freshwater mussel native to western North America, across the majority of its geographical range. We find shallow rangewide genetic structure, strong population‐level structuring and very low population diversity in this species, using both mitochondrial sequence and nuclear microsatellite data. We contrast these patterns with previous findings in another freshwater mussel species group (Anodonta californiensis/A. nuttalliana) occupying the same continental region and many of the same watersheds. We conclude that differences are likely caused by contrasting life history attributes between genera, particularly host fish requirements and hermaphroditism. Further, we demonstrate the occurrence of a ‘hotspot’ for genetic diversity in both groups of mussels, occurring in the vicinity of the lower Columbia River drainage. We suggest that stream hierarchy may be responsible for this pattern and may produce similar patterns in other widespread freshwater species. 相似文献
93.
Qian Lu Chong Wang Rong Pan Xinghua Gao Zhifeng Wei Yufeng Xia Yue Dai 《Journal of cellular biochemistry》2013,114(5):1009-1019
Histamine, a major mediator present in mast cells that is released into the extracellular milieu upon degranulation, is well known to possess a wide range of biological activities in several classic physiological and pathological processes. However, whether and how it participates in angiogenesis remains obscure. In the present study, we observed its direct and synergistic action with basic fibroblast growth factor (bFGF), an important inducer of angiogenesis, on in vitro angiogenesis models of endothelial cells. Data showed that histamine (0.1, 1, 10 µM) itself was absent of direct effects on the processes of angiogenesis, including the proliferation, migration, and tube formation of endothelial cells. Nevertheless, it could concentration‐dependently enhance bFGF‐induced angiogenesis as well as production of vascular endothelial growth factor (VEGF) from endothelial cells. The synergistic effect of histamine on VEGF production could be reversed by pretreatments with diphenhydramine (H1‐receptor antagonist), SB203580 (selective p38 mitogen‐activated protein kinase (MAPK) inhibitor) and L ‐NAME (nitric oxide synthase (NOS) inhibitor), but not with cimetidine (H2‐receptor antagonist) and indomethacin (cyclooxygenase (COX) inhibitor). Moreover, histamine could augment bFGF‐incuced phosphorylation and degradation of IκBα, a key factor accounting for the activation and translocation of nuclear factor κB (NF‐κB) in endothelial cells. These findings indicated that histamine was able to synergistically augment bFGF‐induced angiogenesis, and this action was linked to VEGF production through H1‐receptor and the activation of endothelial nitric oxide synthase (eNOS), p38 MAPK, and IκBα in endothelial cells. J. Cell. Biochem. 114: 1009–1019, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
94.
用RT-PCR方法快速克隆了Wistar大鼠脑神经元特异性烯醇化酶(NSE)的cDNA,将此包括编码全长NSE433个氨基醚的DNA片段重组入pUC质粒,并用PCR方法测定了全部顺序,经重复实验,发现Wistar大鼠与Forss-Petter报导的SD大鼠NSE基因顺序,有两外单碱基的差别,其中一个涉及氨基酸的改变。同时还对RNA的提取及长片段DNA的RT-PCR扩增进行了方法学的探讨。 相似文献
95.
Jiang Chen Huakang Wang Zhengke Wu Hongxia Gu Chong Li Shaolong Wang Guohua Liu 《Animal : an international journal of animal bioscience》2022,16(7):100575
5-Aminolevulinic acid (5-ALA) is an intermediate in haem biosynthesis and has anti-apoptotic, anti-inflammatory, antioxidant, and other pharmacological effects. This study aimed to investigate the effect of dietary supplementation with 5-ALA on growth performance, antioxidant capacity, and inflammatory response of the lipopolysaccharide (LPS)-challenged broiler chickens. The experiment was designed as a 2 × 2 factorial arrangement with dietary 5-ALA (0 or 60 mg/kg) and LPS (injection of saline or 0.5 mg/kg BW) levels as treatments. A total of 240 one-day-old Arbor Acres broilers were distributed into four treatments consisting of six replicates of 10 birds. All the experimental broilers were intraperitoneally injected with LPS or sterile saline at 16, 18, and 20 days of age. Our results showed that dietary 5-ALA supplementation reduced (P < 0.05) the feed to gain before broilers were stimulated with LPS (days 1–15). LPS challenge decreased (P < 0.05) the catalase (CAT), total superoxide dismutase activities and increased the content of malondialdehyde (MDA) in the serum of broiler chickens. However, 5-ALA supplementation had a tendency to increase (P = 0.08) the activity of CAT and decreased (P < 0.05) the content of MDA. LPS challenge showed higher (P < 0.05) interleukin (IL)-1β, IL-6, and IL-10 concentrations in the serum, whereas dietary 5-ALA supplementation decreased (P < 0.05) the levels of IL-1β and IL-6. Additionally, dietary 5-ALA supplementation significantly attenuated (P < 0.05) the upregulation of mRNA expression levels of hepatic toll-like receptor 4 (TLR4), IL-1β, and IL-2 induced by LPS challenge. Moreover, dietary 5-ALA supplementation also enhanced the mRNA expression of 5-aminolevulinate dehydratase, ferrochelatase, and haem oxygenase-1 (HO-1) as compared to the unsupplemented groups. In conclusion, our results suggested that supplementation of 60 mg/kg 5-ALA exhibited LPS-induced anti-inflammatory and antioxidant properties by enhancing the HO-1 expression and inhibiting the TLR4/NF-κB signalling pathway. 相似文献
96.
Yung‐Lin Hsieh Hong‐Yi Kuo Che‐Chang Chang Mandar T Naik Pei‐Hsin Liao Chun‐Chen Ho Tien‐Chi Huang Jen‐Chong Jeng Pang‐Hung Hsu Ming‐Daw Tsai Tai‐Huang Huang Hsiu‐Ming Shih 《The EMBO journal》2013,32(6):791-804
While numerous small ubiquitin‐like modifier (SUMO) conjugated substrates have been identified, very little is known about the cellular signalling mechanisms that differentially regulate substrate sumoylation. Here, we show that acetylation of SUMO E2 conjugase Ubc9 selectively downregulates the sumoylation of substrates with negatively charged amino acid‐dependent sumoylation motif (NDSM) consisting of clustered acidic residues located downstream from the core ψ‐K‐X‐E/D consensus motif, such as CBP and Elk‐1, but not substrates with core ψ‐K‐X‐E/D motif alone or SUMO‐interacting motif. Ubc9 is acetylated at residue K65 and K65 acetylation attenuates Ubc9 binding to NDSM substrates, causing a reduction in NDSM substrate sumoylation. Furthermore, Ubc9 K65 acetylation can be downregulated by hypoxia via SIRT1, and is correlated with hypoxia‐elicited modulation of sumoylation and target gene expression of CBP and Elk‐1 and cell survival. Our data suggest that Ubc9 acetylation/deacetylation serves as a dynamic switch for NDSM substrate sumoylation and we report a previously undescribed SIRT1/Ubc9 regulatory axis in the modulation of protein sumoylation and the hypoxia response. 相似文献
97.
Microsatellite genetic variation in the Chinese endemic Eucommia ulmoides (Eucommiaceae): implications for conservation 总被引:1,自引:0,他引:1
Jinju Zhang Chong Xing Hua Tian Xiaohong Yao 《Botanical journal of the Linnean Society. Linnean Society of London》2013,173(4):775-785
Eucommia ulmoides, a traditional Chinese medicinal plant, is endangered as a consequence of long‐term and widespread harvest in the late 20th century. It has been widely cultivated as a source of herbal medicine and for use in the organic chemical industry in China. In this study, eight microsatellite markers were applied to investigate genetic diversity in E. ulmoides. Three hundred individuals from one semi‐wild population and nine cultivated populations across its main production area were collected. A high level of genetic diversity at population levels (HE = 0.716) was observed. The highly outcrossed mating system, high longevity of E. ulmoides and seed admixture may be responsible for high genetic variation within populations. A genetic bottleneck was observed in one population. Populations were only slightly differentiated from one another (FST = 0.063); this was also supported by AMOVA, which revealed that 94.05% of the total variation resided within populations. This is probably attributable to long‐distance gene flow mediated by the exchange of seeds by local farmers. Implications of these results for the conservation of genetic resources of E. ulmoides are discussed. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013, 173 , 775–785. 相似文献
98.
Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II 总被引:1,自引:0,他引:1
Defensins constitute a major class of cationic antimicrobial peptides in mammals and vertebrates, acting as effectors of innate immunity against infectious microorganisms. It is generally accepted that defensins are bactericidal by disrupting the anionic microbial membrane. Here, we provide evidence that membrane activity of human α-defensins does not correlate with antibacterial killing. We further show that the α-defensin human neutrophil peptide-1 (HNP1) binds to the cell wall precursor lipid II and that reduction of lipid II levels in the bacterial membrane significantly reduces bacterial killing. The interaction between defensins and lipid II suggests the inhibition of cell wall synthesis as a novel antibacterial mechanism of this important class of host defense peptides. 相似文献
99.
Kuankuan Ai Yanli Jia Jin Li Chong Wang Yan Wang 《Journal of cellular biochemistry》2019,120(5):8069-8077
Gastric cancer (GC) is the second most common cause of cancer death worldwide but could be more curable if diagnosed at an earlier stage. At present, the capability to predict the efficaciousness of molecular diagnosis for GC for each patient remains elusive. The purpose of this study was to identify tumor biomarkers through systems analysis of multigene predictors exploiting the available data resource. In this study, we investigated the top 10% overexpressed genes in GC from five data sets of the Oncomine platform, with 265 GC samples versus 174 normal gastric mucosa samples. Sixteen candidate genes were identified as predictors of GC, of which 14 genes were verified through the comparison of expression levels in specimens from normal (chronic gastritis, 21 samples) and GC groups (38 samples). In addition, unique molecular portraits of diffuse adenocarcinoma (DA), intestinal adenocarcinoma (IA), and mixed adenocarcinoma (MA) were studied through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, where DA showed higher extracellular matrix alteration while IA and MA showed higher cell-cycle alteration than other types. We also found that the elevated expressions of genes during GC progression were independent of gene mutations, and high core-binding factor subunit β expression is correlated with a high overall survival rate in GC patients. Our research may provide an efficient clinical diagnosis of GC at an early stage with high accuracy and thus help improve the overall survival rate through early therapeutic interventions. 相似文献
100.