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41.
Sigong Zhang Xueqin Jia Qiuyue Zhang Li Zhang Jing Yang Caihong Hu Junnian Shi Xiao Jiang Jinyue Lu Haili Shen 《Journal of cellular and molecular medicine》2020,24(2):1658-1669
Excessive neutrophil extracellular trap (NET) formation may contribute to polymyositis (PM)‐associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. In this study, we found that NET accelerated the progression of ILD and promoted pulmonary fibrosis (PF) in vivo. miR‐7 expression was down‐regulated in lung tissue of PM group than control group, and NETs further decreased miR‐7 expression. TLR9 and Smad2 were up‐regulated in lung tissue of PM group than control group, and NETs further increased TLR9 and Smad2 expressions. In vitro experiments showed that PMA‐treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNase I decreased the promotion effect of NETs. Neutrophil extracellular trap components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR‐7 and Smad2 in LF. Finally, miR‐7‐Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. Therefore, NETs promote PM‐related ILD, and TLR9‐miR‐7‐Smad2 signalling pathway is involved in the proliferation of LFs and their differentiation into MFs. 相似文献
42.
目的:调查油田野外作业工人慢性疾病患病情况,分析职业紧张与神经递质的相关性。方法:通过整群抽样的方式选取油田野外作业工人2000例作为研究对象,采用自制的慢性非传染性疾病调查量表对所有工人的慢性疾病情况予以调查,采用职业紧张量表对所有工人的职业紧张情况予以调查。采用酶联免疫吸附法检测所有工人血清五羟色胺、去甲肾上腺素以及神经肽Y水平,并采用偏相关分析油田野外作业工人职业紧张与神经递质的相关性。结果:2000例油田野外作业工人慢性疾病发病率最高的前三种疾病分别为颈腰部疾病、高血压、高血脂,占比分别为20.60%、15.35%、11.20%。油田野外作业工人中男性职业任务、个体应对资源评分高于女性,而锻炼工人的个体紧张反应评分低于不锻炼工人(P0.05)。油田野外作业工人中饮酒工人神经肽Y水平低于不饮酒工人,锻炼工人的去甲肾上腺素水平高于不锻炼工人(P0.05)。经偏相关分析可得:油田野外作业工人的职业任务评分与五羟色胺、去甲肾上腺素水平呈正相关(P0.05),个体紧张反应评分与神经肽Y水平呈负相关(P0.05)。结论:油田野外作业工人慢性疾病患病情况不容乐观,且其职业紧张与神经递质存在密切相关,在临床工作中可通过改善油田野外作业工人的职业紧张,从而达到改善其神经递质水平的目的。 相似文献
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Chloé Dussault-Benoit Geneviève Arsenault-Labrecque Humira Sonah François Belzile Richard R. Bélanger 《Molecular Plant Pathology》2020,21(3):318-329
The soybean–Phytophthora sojae interaction operates on a gene-for-gene relationship, where the product of a resistance gene (Rps) in the host recognizes that of an avirulence gene (Avr) in the pathogen to generate an incompatible reaction. To exploit this form of resistance, one must match with precision the appropriate Rps gene with the corresponding Avr gene. Currently, this association is evaluated by phenotyping assays that are labour-intensive and often imprecise. To circumvent this limitation, we sought to develop a molecular assay that would reveal the avirulence allele of the seven main Avr genes (Avr1a, Avr1b, Avr1c, Avr1d, Avr1k, Avr3a, and Avr6) in order to diagnose with precision the pathotypes of P. sojae isolates. For this purpose, we analysed the genomic regions of these Avr genes in 31 recently sequenced isolates with different virulence profiles and identified discriminant mutations between avirulence and virulence alleles. Specific primers were designed to generate amplicons of a distinct size, and polymerase chain reaction conditions were optimized in a final assay of two parallel runs. When tested on the 31 isolates of known virulence, the assay accurately revealed all avirulence alleles. The test was further assessed and compared to a phenotyping assay on 25 isolates of unknown virulence. The two assays matched in 97% (170/175) of the interactions studied. Interestingly, the sole cases of discrepancy were obtained with Avr3a, which suggests a possible imperfect interaction with Rps3a. This molecular assay offers a powerful and reliable tool to exploit and study with greater precision soybean resistance against P. sojae. 相似文献
46.
Accumulation of PINK1 on the outer mitochondrial membrane (OMM) is necessary for PINK‐mediated mitophagy. The proton ionophores, like carbonyl cyanide m‐chlorophenylhydrazone (CCCP) and carbonyl cyanide‐4‐(trifluoromethoxy)phenylhydrazone (FCCP), inhibit PINK1 import into mitochondrial matrix and induce PINK1 OMM accumulation. Here, we show that the CHCHD4/GFER disulfide relay system in the mitochondrial intermembrane space (IMS) is required for PINK1 stabilization when mitochondrial membrane potential is lost. Activation of CHCHD4/GFER system by mitochondrial oxidative stress or inhibition of CHCHD4/GFER system with antioxidants can promote or suppress PINK1 accumulation, respectively. Thus data suggest a pivotal role of CHCHD4/GFER system in PINK1 accumulation. The amyotrophic lateral sclerosis‐related superoxide dismutase 1 mutants dysregulated redox state and CHCHD4/GFER system in the IMS, leading to inhibitions of PINK1 accumulation and mitophagy. Thus, the redox system in the IMS is involved in PINK1 accumulation and damaged mitochondrial clearance, which may play roles in mitochondrial dysfunction‐related neurodegenerative diseases. 相似文献
47.
Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models
Heesun Choi Haeng Jun Kim Jinhee Yang Sehyun Chae Wonik Lee Sunwoo Chung Jisoo Kim Hyunjung Choi Hyeseung Song Chang Kon Lee Jae Hyun Jun Yong Jae Lee Kyunghyeon Lee Semi Kim Hye‐ri Sim Young Il Choi Keun Ho Ryu Jong‐Chan Park Dongjoon Lee Sun‐Ho Han Daehee Hwang Jangbeen Kyung Inhee Mook‐Jung 《Aging cell》2020,19(1)
Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD‐504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLPAPT) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient‐derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau‐interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLPAPT mice. 相似文献
48.
《Saudi Journal of Biological Sciences》2020,27(10):2839-2846
Non-destructive methods have been widely recognized for evaluating fruit quality traits of many horticultural crops and food processing industry. Destructive (analytical) test, and non-destructive evaluation of the quality traits were investigated and compared for ‘Red Rose’ tomato (Solanum lycopersicum L.) fruit grown under protected environment. Fresh tomato fruit at five distinctive maturity stages namely; breaker (BK), turning (TG), pink (PK), light-red (LR), and red (RD) were labeled and scanned using the handheld near infra-red (NIR) enhanced spectrometer at a wavelength range of 285–1200 nm. The labeled tomato samples were then measured analytically for flesh firmness, lycopene, β-carotene, total phenolic content (TPC) and total flavonoids content (TFC). The results revealed that quality traits could be estimated using NIR spectroscopy with a relatively high coefficient of determination (R2): 0.834 for total phenolic content, 0.864 for lycopene, 0.790 for total flavonoid content, 0.708 for β-carotene; and 0.679 for flesh firmness. The accumulation of Lyco and β-Car rapidly increased in tomatoes harvested between the TG and the LR maturity stages. Harvesting tomatoes at BK maturity stage resulted in significantly higher flesh firmness than harvesting at the later maturity stages. Tomato fruits had the lowest TPC and TFC contents at the earliest maturity stage (BK), while they had intermediate TPC and TFC levels at LR and RD maturity stages. NIR spectroscopic measurements of fruit firmness and lipophilic antioxidants in tomato fruit at various maturity stages were partially in accordance with those estimated by destructive (analytical) methods. Based on these findings, we recommend using non-destructive NIR spectroscopy as an effective tool for predicting tomato fruit quality during harvest stage and postharvest processing. 相似文献
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《Bioorganic & medicinal chemistry letters》2020,30(17):127370
Multitargeted ligands have demonstrated remarkable efficiency as potential therapeutics for neurodegenerative diseases as they target multiple pathways involved in the progression of these diseases. Herein, we report first-in-class dual inhibitor of acetylcholinesterase (AChE) and tau aggregation as a novel class of multitargeted ligands for neurodegenerative diseases. The reported biphenyl pyrazole scaffold binds monomeric tau with submicromolar affinity and impedes the formation of tau oligomers at early stages. Additionally, the lead compound inhibited AChE activity with an IC50 value of 0.35 ± 0.02 μM. Remarkably, the neuroprotective effect of this lead in induced cytotoxicity model of SH-SY5Y neuroblastoma cells is superior to single-targeted AChE and tau-aggregation inhibitors. This scaffold would enable development of new generation of multitargeted ligands for neurodegenerative diseases that function through dual targeting of AChE and monomeric tau. 相似文献