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61.
ChiWei Yeh WeiChieh Huang PangHung Hsu KunHai Yeh LiChin Wang Paul WeiChe Hsu HsiuChuan Lin YiNing Chen ShuChuan Chen ChenHsiang Yeang HsuehChi S Yen 《The EMBO journal》2021,40(7)
Protein termini are determinants of protein stability. Proteins bearing degradation signals, or degrons, at their amino‐ or carboxyl‐termini are eliminated by the N‐ or C‐degron pathways, respectively. We aimed to elucidate the function of C‐degron pathways and to unveil how normal proteomes are exempt from C‐degron pathway‐mediated destruction. Our data reveal that C‐degron pathways remove mislocalized cellular proteins and cleavage products of deubiquitinating enzymes. Furthermore, the C‐degron and N‐degron pathways cooperate in protein removal. Proteome analysis revealed a shortfall in normal proteins targeted by C‐degron pathways, but not of defective proteins, suggesting proteolysis‐based immunity as a constraint for protein evolution/selection. Our work highlights the importance of protein termini for protein quality surveillance, and the relationship between the functional proteome and protein degradation pathways. 相似文献
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Kamal Laina Zarisa Mohd Adam Mowaffaq Adam Ahmed Shahpudin Siti Nurfatimah Mohd. Shuib Ahmad Naqeeb Sandai Rosline Hassan Norazian Mohd Tabana Yasser Basri Dayang Fredalina Than Leslie Thian Lung Sandai Doblin 《Mycopathologia》2021,186(2):221-236
Mycopathologia - Candida albicans has been reported globally as the most widespread pathogenic species contributing candidiasis from superficial to systemic infections in immunocompromised... 相似文献
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A new species of rugose coral, Sanidophyllum dubium n. sp., and the typical Emsian (Early Devonian) rugose coral Xystriphylloides nobilis are described from the Mia Le Formation in northern Vietnam. The lower Emsian index conodonts ranging from the Polygnathus excavatus zone to the P. nothoperbonus zone are illustrated. The biostratigraphic correlation between northern Vietnam and South China shows that the Mia Le Formation in northern Vietnam is early Emsian in age, and its upper part can be correlated with the lower part of the Shizhou Member of the Yukiang Formation in Liujing, Guangxi and its equivalents in South China. Based on the study of the lower Emsian biostratigraphic sequence, the disappearance of Xystriphylloides nobilis fauna in the overlying bed of the uppermost Mia Le Formation and the extinction of the “tonkinensis fauna” (sensu lato) in the interval between the basal Si Phai Formation and the uppermost Mia Le Formation demonstrate the influence of the Yujiang Event in northern Vietnam. 相似文献
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Liangmiao Wu Xinhua Zhou Yiwan Cao Shing Hung MAK Ling Zha Ning Li Zhiyang Su Yifan Han Yuqiang Wang Maggie Pui Man Hoi Yewei Sun Gaoxiao Zhang Zaijun Zhang Xifei Yang 《Aging cell》2021,20(6)
Alzheimer''s disease (AD) is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited. Over‐activation of N‐methyl‐D‐aspartate (NMDA) receptors, amyloid β (Aβ) aggregation, a decrease in cerebral blood flow (CBF), and downstream pathological events play important roles in the disease progression of AD. In the present study, MN‐08, a novel memantine nitrate, was found to inhibit Aβ accumulation, prevent neuronal and dendritic spine loss, and consequently attenuate cognitive deficits in 2‐month‐old APP/PS1 transgenic mice (for a 6‐month preventative course) and in the 8‐month‐old triple‐transgenic (3×Tg‐AD) mice (for a 4‐month therapeutic course). In vitro, MN‐08 could bind to and antagonize NMDA receptors, inhibit the calcium influx, and reverse the dysregulations of ERK and PI3K/Akt/GSK3β pathway, subsequently preventing glutamate‐induced neuronal loss. In addition, MN‐08 had favorable pharmacokinetics, blood‐brain barrier penetration, and safety profiles in rats and beagle dogs. These findings suggest that the novel memantine nitrate MN‐08 may be a useful therapeutic agent for AD. 相似文献
66.
ShuChun Kuo ChungChing Chio ChaoHung Yeh JuiTi Ma WenPin Liu MaoTsun Lin KaoChang Lin ChingPing Chang 《Aging cell》2021,20(5)
Amyloid‐beta (Aβ) oligomer is known to contribute to the pathophysiology of age‐related macular degeneration. Herein, we aimed to elucidate the in vivo and in vitro effects of Aβ1‐42 application on retinal morphology in rats. Our in vivo studies revealed that intracerebroventricular administration of Aβ1‐42 oligomer caused dysmorphological changes in both retinal ganglion cells and retinal pigment epithelium. In addition, in vitro studies revealed that ARPE‐19 cells following Aβ1‐42 oligomer application had decreased viability along with apoptosis and decreased expression of the tight junction proteins, increased expression of both phosphor‐AKT and phosphor‐GSK3β and decreased expression of both SIRT1 and β‐catenin. Application of conditioned medium (CM) obtained from mesenchymal stem cells (MSC) protected against Aβ1‐42 oligomer‐induced retinal pathology in both rats and ARPE‐19 cells. In order to explore the potential role of peptides secreted from the MSCs, we applied mass spectrometry to compare the peptidomics profiles of the MSC‐CM. Gene ontology enrichment analysis and String analysis were performed to explore the differentially expressed peptides by predicting the functions of their precursor proteins. Bioinformatics analysis showed that 3‐8 out of 155–163 proteins in the MSC‐CM maybe associated with SIRT1/pAKT/pGSK3β/β‐catenin, tight junction proteins, and apoptosis pathway. In particular, the secretomes information on the MSC‐CM may be helpful for the prevention and treatment of retinal pathology in age‐related macular degeneration. 相似文献
67.
Dieu T. X. Nguyen Hung Tran Stefan Schwaiger Hermann Stuppner Stefania Marzocco 《化学与生物多样性》2021,18(1):e2000577
The extract of Elsholtzia ciliata aerial parts was subjected to bio-guided isolation using the intercellular ROS reduction in J774A.1 macrophages to monitor the anti-oxidative activity. Fifteen compounds were isolated from the active fractions including eleven flavonoids (vitexin, pedalin, luteolin-7-O-β-d -glucopyranoside, apigenin-5-O-β-d -glucopyranoside, apigenin-7-O-β-d -glucopyranoside, chrysoeriol-7-O-β-d -glucopyranoside, 7,3′-dimethoxyluteolin-6-O-β-d -glucopyranoside, luteolin, 5,6,4′-trihydroxy-7,3′-dimethoxyflavone, 5-hydroxy-6,7-dimethoxyflavone (compound 13 ), 5-hydroxy-7,8-dimethoxyflavone); three hydroxycinnamic acid derivatives (caffeic acid, 4-(E)-caffeoyl-l -threonic acid, 4-O-(E)-p-coumaroyl-l -threonic acid) and one fatty acid (α-linolenic acid). The biological evaluation of these compounds (10–2.5 μm ) indicated that all of them exerted good antioxidant and anti-inflammatory activities, in particular compound 13 . 相似文献
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Kai Hung Tiong Li Yen Mah Chee-Onn Leong 《Apoptosis : an international journal on programmed cell death》2013,18(12):1447-1468
The fibroblast growth factor receptors (FGFRs) regulate important biological processes including cell proliferation and differentiation during development and tissue repair. Over the past decades, numerous pathological conditions and developmental syndromes have emerged as a consequence of deregulation in the FGFRs signaling network. This review aims to provide an overview of FGFR family, their complex signaling pathways in tumorigenesis, and the current development and application of therapeutics targeting the FGFRs signaling for treatment of refractory human cancers. 相似文献