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101.
102.
Ze Yu Hao Wang Yilin Fang Liangliang Lu Minghao Li Bingru Yan Yuzhe Nie Chunbo Teng 《Journal of cellular biochemistry》2020,121(3):2318-2329
Heat shock proteins (HSPs) were known as the molecular chaperones, which play a pivotal role in the protein quality control system, ensuring correct folding of proteins, and facilitating the correct refolding of damaged proteins via the transient interaction with their substrate proteins. They also practice in the regulation of cell cycles and are involved in apoptosis. We found that HspB2 was almost completely silent in pancreatic cancer and few studies investigated the role of HspB2 in cancer cells, particularly in pancreatic cancer. Here, we reported that HspB2 effectively inhibited cell proliferation in Panc-1 cells. Specifically, we demonstrated that HspB2 could combine mut-p53 and change the DNA binding site of mutant p53, subsequently upregulated the expression of RPRM, BAI-1, and TSAP6 which were the downstream genes of wt-p53, participate in mediating downstream responses to p53, including inhibiting cell proliferation and angiogenesis. The main aim of this study is to investigate the relationship between HspB2 and p53, and provide a novel treatment strategy for pancreatic cancer. 相似文献
103.
Three‐dimensional (3D) stem cell differentiation cultures recently emerged as a novel model system for investigating human embryonic development and disease progression in vitro, complementing existing animal and two‐dimensional (2D) cell culture models. Organoids, the 3D self‐organizing structures derived from pluripotent or somatic stem cells, can recapitulate many aspects of structural organization and functionality of their in vivo organ counterparts, thus holding great promise for biomedical research and translational applications. Importantly, faithful recapitulation of disease and development processes relies on the ability to modify the genomic contents in organoid cells. The revolutionary genome engineering technologies, CRISPR/Cas9 in particular, enable investigators to generate various reporter cell lines for prompt validation of specific cell lineages as well as to introduce disease‐associated mutations for disease modeling. In this review, we provide historical overviews, and discuss technical considerations, and potential future applications of genome engineering in 3D organoid models. 相似文献
104.
When Escherichia coli is grown on oleic acid as the sole carbon source, most of this fatty acid is completely degraded by beta-oxidation. However, approximately 10% of the oleic acid is only partially degraded to 3,5- cis-tetradecadienoyl-CoA, which is hydrolyzed to 3,5- cis-tetradecadienoic acid and released into the growth medium. An investigation of thioesterases involved in this novel pathway of beta-oxidation led to the identification of a new thioesterase (thioesterase III) that is induced by growth of E. coli on oleic acid. This enzyme was partially purified and identified as the ybaW gene product by mass spectrometric analysis of tryptic peptides. The ybaW gene, which has a putative consensus sequence for binding the fatty acid degradation repressor, was cloned and expressed in E. coli. Thioesterase III was shown to be a long-chain acyl-CoA thioesterase that is most active with 3,5-tetradecadienoyl-CoA, a minor metabolite of oleate beta-oxidation. Its substrate specificity and induction by fatty acids agree with its proposed function in the thioesterase-dependent pathway of beta-oxidation. Thioesterase III is proposed to hydrolyze metabolites of beta-oxidation that are resistant to further degradation and that would inhibit the flux through the pathway if they were allowed to accumulate. 相似文献
105.
Rapid development, transparency and small size are the outstanding features of zebrafish that make it as an increasingly important vertebrate system for developmental biology, functional genomics, disease modeling and drug discovery. Zebrafish has been regarded as ideal animal specie for studying the relationship between genotype and phenotype, for pathway analysis and systems biology. However, the tremendous amount of data generated from large numbers of embryos has led to the bottleneck of data analysis and modeling. The zebrafish image quantitator (ZFIQ) software provides streamlined data processing and analysis capability for developmental biology and disease modeling using zebrafish model. AVAILABILITY: ZFIQ is available for download at http://www.cbi-platform.net. 相似文献
106.
Background
In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects’ psychological attitude to acupuncture and their physical state are the three most confounding factors.Objective
To obtain more precise and accurate cerebral fMRI mapping of acupuncture.Design and Setting
A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China.Participants
Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D.Interventions
Group A received real acupuncture (RA) and treatment instruction (TI); Group B received RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and TI; Group D received SA and NI.Results
Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas.Conclusions
The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results. 相似文献107.
Panaxynol, a polyacetylene ((3R)-heptadeca-1,9-diene-4,6-diyn-3-ol; syn. falcarinol), was isolated from the lipophilic fractions of Panax notoginseng, a Chinese traditional medicinal plant. In the present study, we reported the neurotrophic effects of panaxynol on PC12D cells and mechanism involved in neurite outgrowth of the cells. Panaxynol could morphologically promote neurite outgrowth in PC12D cells, concentration-dependently reduce cell division and up-regulate molecular marker (MAP1B) expression in PC12D cells. Panaxynol induces the elevation of intracellular cAMP in PC12D cells. The neurite outgrowth in PC12D cells induced by panaxynol could be inhibited by the protein kinase A inhibitor RpcAMPS and by MAP kinase kinase 1/2 inhibitor U0126. These observations reveal that panaxynol could induce the differentiation of PC12D cells in a process similar to but distinct from that of NGF and the panaxynol's effects were via cAMP- and MAP kinase-dependent mechanisms. 相似文献
108.
Groups of distinct but related diseases often share common symptoms, which suggest likely overlaps in underlying pathogenic mechanisms. Identifying the shared pathways and common factors among those disorders can be expected to deepen our understanding for them and help designing new treatment strategies effected on those diseases. Neurodegeneration diseases, including Alzheimer''s disease (AD), Parkinson''s disease (PD) and Huntington''s disease (HD), were taken as a case study in this research. Reported susceptibility genes for AD, PD and HD were collected and human protein-protein interaction network (hPPIN) was used to identify biological pathways related to neurodegeneration. 81 KEGG pathways were found to be correlated with neurodegenerative disorders. 36 out of the 81 are human disease pathways, and the remaining ones are involved in miscellaneous human functional pathways. Cancers and infectious diseases are two major subclasses within the disease group. Apoptosis is one of the most significant functional pathways. Most of those pathways found here are actually consistent with prior knowledge of neurodegenerative diseases except two cell communication pathways: adherens and tight junctions. Gene expression analysis showed a high probability that the two pathways were related to neurodegenerative diseases. A combination of common susceptibility genes and hPPIN is an effective method to study shared pathways involved in a group of closely related disorders. Common modules, which might play a bridging role in linking neurodegenerative disorders and the enriched pathways, were identified by clustering analysis. The identified shared pathways and common modules can be expected to yield clues for effective target discovery efforts on neurodegeneration. 相似文献
109.
Xia Zhao Shuangshuang Lu Junwei Nie Xiaoshan Hu Wen Luo Xiangqi Wu Hailang Liu Qiuting Feng Zai Chang Yaoqiu Liu Yunshan Cao Haixiang Sun Xinli Li Yali Hu Zhongzhou Yang 《Molecular and cellular biology》2014,34(11):1966-1975
The protein kinase Akt plays a critical role in heart function and is activated by phosphorylation of threonine 308 (T308) and serine 473 (S473). While phosphoinositide-dependent kinase 1 (PDK1) is responsible for Akt T308 phosphorylation, the identities of the kinases for Akt S473 phosphorylation in the heart remain controversial. Here, we disrupted mTOR complex 2 (mTORC2) through deletion of Rictor in the heart and found normal heart growth and function. Rictor deletion caused significant reduction of Akt S473 phosphorylation but enhanced Akt T308 phosphorylation, suggesting that a high level of Akt T308 phosphorylation maintains Akt activity and heart function. Deletion of Pdk1 in the heart caused significantly enhanced Akt S473 phosphorylation that was suppressed by removal of Rictor, leading to worsened dilated cardiomyopathy (DCM) and accelerated heart failure in Pdk1-deficient mice. In addition, we found that increasing Akt S473 phosphorylation through deletion of Pten or chemical inhibition of PTEN reversed DCM and heart failure in Pdk1-deficient mice. Investigation of heart samples from human DCM patients revealed changes similar to those in the mouse models. These results demonstrated that PDK1 and mTORC2 synergistically promote postnatal heart growth and maintain heart function in postnatal mice. 相似文献
110.