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81.
Xian-Hui Dong Dong-Xue Ma Tian-Ci Zhang Xiao-Ping He Li-Jun Xu Ya-Lei Liu Hao Li Wei-Juan Gao 《Neurochemical research》2021,46(5):1068-1080
Neurochemical Research - Alzheimer’s disease (AD) process is characterized classically by two hallmark pathologies: β-amyloid (Aβ) plaque deposition and neurofibrillary tangles of... 相似文献
82.
Wei Liu Yaoting Sun Weigang Ge Fangfei Zhang Lin Gan Yi Zhu Tiannan Guo Kexin Liu 《Molecular & cellular proteomics : MCP》2022,21(2):100187
Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR. 相似文献
83.
84.
In the adult murine brain, the microtubule-associated protein tau exists as three major isoforms, which have four microtubule-binding repeats (4R), with either no (0N), one (1N) or two (2N) amino-terminal inserts. The human brain expresses three additional isoforms with three microtubule-binding repeats (3R) each. However, little is known about the role of the amino-terminal inserts and how the 0N, 1N and 2N tau species differ. In order to investigate this, we generated a series of isoform-specific antibodies and performed a profiling by Western blotting and immunohistochemical analyses using wild-type mice in three age groups: two months, two weeks and postnatal day 0 (P0). This revealed that the brain is the only organ to express tau at significant levels, with 0N4R being the predominant isoform in the two month-old adult. Subcellular fractionation of the brain showed that the 1N isoform is over-represented in the soluble nuclear fraction. This is in agreement with the immunohistochemical analysis as the 1N isoform strongly localizes to the neuronal nucleus, although it is also found in cell bodies and dendrites, but not axons. The 0N isoform is mainly found in cell bodies and axons, whereas nuclei and dendrites are only slightly stained with the 0N antibody. The 2N isoform is highly expressed in axons and in cell bodies, with a detectable expression in dendrites and a very slight expression in nuclei. The 2N isoform that was undetectable at P0, in adult brain was mainly found localized to cell bodies and dendrites. Together these findings reveal significant differences between the three murine tau isoforms that are likely to reflect different neuronal functions. 相似文献
85.
Hanhan Liu Qiangqiang Jia Gianluca Tettamanti Sheng Li 《Insect biochemistry and molecular biology》2013,43(11):1068-1078
In the fruitfly, Drosophila melanogaster, autophagy and caspase activity function in parallel in the salivary gland during metamorphosis and in a common regulatory hierarchy during oogenesis. Both autophagy and caspase activity progressively increase in the remodeling fat body, and they are induced by a pulse of the molting hormone (20-hydroxyecdysone, 20E) during the larval-prepupal transition. Inhibition of autophagy and/or caspase activity in the remodeling fat body results in 25–40% pupal lethality, depending on the genotypes. Interestingly, a balancing crosstalk occurs between autophagy and caspase activity in this tissue: the inhibition of autophagy induces caspase activity and the inhibition of caspases induces autophagy. The Drosophila remodeling fat body provides an in vivo model for understanding the molecular mechanism of the balancing crosstalk between autophagy and caspase activity, which oppose with each other and are induced by the common stimulus 20E, and blockage of either path reinforces the other path. 相似文献
86.
Xiao-Long Lin Yan-Min Zhao Li-Ping Yan Wen-Bin Liu Wen-Jun Bu Xin-Hua Wang Chen-Guang Zheng 《Zoologica scripta》2022,51(1):119-132
Evolutionary analysis of Prodiamesinae has long been impeded by lack of information, and its phylogenetic relationship with Orthocladiinae remains questionable. Here, ten complete mitochondrial genomes (mitogenomes) of Orthocladiinae sensu lato were newly sequenced, including three Prodiamesinae species and seven Orthocladiinae species. Coupled with published mitogenomes, a total of 12 mitogenomes of Orthocladiinae sensu lato were selected for a comparative mitogenomic analysis and phylogenetic reconstruction. Mitogenomes of Orthocladiinae sensu lato are conserved in structure, and all genes arrange the same gene order as the ancestral insect mitogenome. Nucleotide composition is highly biased, and the control region displayed the highest A + T content. All protein-coding genes are under purifying selection, and the ATP8 evolves at the fastest rate. In addition, the mitogenomes of Orthocladiinae sensu lato are highly conserved, and they are practically useful for phylogenetic inference, suggesting a re-classification of Orthocladiinae by sinking Prodiamesinae as a subgroup of Orthocladiinae. 相似文献
87.
Guohong Liu Bo Liu Naiquan Lin Weiqi Tang Jianyang Tang Yingzhi Lin 《Journal of bacteriology》2012,194(23):6633
Bacillus sp. strain FJAT-13831 was isolated from the no. 1 pit soil of Emperor Qin''s Terracotta Warriors in Xi''an City, People''s Republic of China. The isolate showed a close relationship to the Bacillus cereus group. The draft genome sequence of Bacillus sp. FJAT-13831 was 4,425,198 bp in size and consisted of 5,567 genes (protein-coding sequences [CDS]) with an average length of 782 bp and a G+C value of 36.36%. 相似文献
88.
Mingcheng Qian Xinyu Jiang Mingting Zhang Lijuan Hu Huimin Liu Shuai Zhao Xiaoying Zhou Xin Chen 《化学与生物多样性》2021,18(4):e2000979
In this article, we designed and synthesized two series of matrine analogs with ring-opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analog N-(3-bromophenyl)-4-[(1R,3aS,10aR,10bS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl]butanamide ( B11 ) with a meta-bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose-dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert-butyl (1R,3aS,10aR,10bS)-1-[4-(3-bromoanilino)-4-oxobutyl]octahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridine-2(3H)-carboxylate ( A11 , an analog of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potential anticancer lead compound B11 , which can be used for further study both in vitro and in vivo. 相似文献
89.
S S Bo?ko V P Zherdev A A Dvorianinov I Janku E Buchar 《Biulleten' eksperimental'no? biologii i meditsiny》1990,110(11):501-503
Pharmacokinetics of novel immunostimulating drug kamantane was studied by using gas-liquid chromatography in experiments on rats. It was found that kemantane biotransformed rapidly after oral administration with the forming of active metabolite. Kemantane and its metabolites are distributed rapidly from the blood to organs. The drug is eliminated from the organism of rats as metabolite. 相似文献
90.
Bo Lin Dipika Gupta Christopher D. Heinen 《The Journal of biological chemistry》2014,289(35):24314-24324
Human pluripotent stem cells (PSCs) are presumed to have robust DNA repair pathways to ensure genome stability. PSCs likely need to protect against mutations that would otherwise be propagated throughout all tissues of the developing embryo. How these cells respond to genotoxic stress has only recently begun to be investigated. Although PSCs appear to respond to certain forms of damage more efficiently than somatic cells, some DNA damage response pathways such as the replication stress response may be lacking. Not all DNA repair pathways, including the DNA mismatch repair (MMR) pathway, have been well characterized in PSCs to date. MMR maintains genomic stability by repairing DNA polymerase errors. MMR is also involved in the induction of cell cycle arrest and apoptosis in response to certain exogenous DNA-damaging agents. Here, we examined MMR function in PSCs. We have demonstrated that PSCs contain a robust MMR pathway and are highly sensitive to DNA alkylation damage in an MMR-dependent manner. Interestingly, the nature of this alkylation response differs from that previously reported in somatic cell types. In somatic cells, a permanent G2/M cell cycle arrest is induced in the second cell cycle after DNA damage. The PSCs, however, directly undergo apoptosis in the first cell cycle. This response reveals that PSCs rely on apoptotic cell death as an important defense to avoid mutation accumulation. Our results also suggest an alternative molecular mechanism by which the MMR pathway can induce a response to DNA damage that may have implications for tumorigenesis. 相似文献