This mini-review will schematically update the progress of the expanding Mi-2/Nucleosome Remodeling Deacetylase (NuRD) complexes in cancer and in normal development such as stemness, with a focus on mammals and the increasingly popular and powerful model organism Caenorhabditis elegans. The Mi-2/NuRD complexes control gene activity during the development of complex organisms. Every Mi-2/NuRD complex contains many different core polypeptides, which form distinct multifunctional complexes with specific context-dependent regulators. The Mi-2/NuRD complexes have unique ATP-dependent chromatin remodeling, histone deacetylase, demethylase activities and higher order chromatin organization. They can regulate the accessibility of transcription factors or repair proteins to DNA. In this review, we summarize our current knowleges in the composition, interaction and function of the subunits within the Mi-2/NuRD complex, the methodology used for the identification of Mi-2/NuRD complexes, as well as the clinical and therapeutic implications targeting the Mi-2/NuRD subunits.
Background: To optimize [ 18 F] 9-fluoropropyl-(+)-dihydrotetrabenazine ( 18 F-FP-(+)-DTBZ) purification via solid-phase extraction (SPE) with combined cartridges to facilitate its widespread clinical application. Methods: A modified SPE purification method, employing Sep-Pak PS-2 and Sep-Pak C18 cartridges, was used for the preparation of 18 F-FP-(+)-DTBZ. This method was compared to the purification method of high-pressure liquid chromatography (HPLC) and SPE with one cartridge, following quality control test and positron emission tomography (PET) imaging in healthy volunteers and patients with parkinsn's disease (PD). Results: A SPE purification method integrating Sep-Pak PS-2 and Sep-Pak C18 cartridges was implemented successfully. The retention time of 18 F-FP-(+)-DTBZ purified by HPLC, SPE with Sep-Pak PS-2, SPE with Sep-Pak C18, and SPE with combined use of Sep-Pak PS-2 and Sep-Pak C18 cartridges was 8.7, 8.8, 8.7, and 8.9 min, respectively. Fewest impurity peak was detected in 18 F-FP-(+)-DTBZ purified by the SPE with combined use of Sep-Pak PS-2 and Sep-Pak C18 cartridges. This modified SPE purification method provided a satisfactory radiochemical yield of 29 ± 1.8% with radiochemical purity >99% and shortened synthesis time to 27 min. The brain uptake of 18 F-FP-(+)-DTBZ purified by the modified SPE was comparable to that purified by HPLC in both healthy volunteers and PD patients. Conclusions: A SPE method integrating Sep-Pak PS-2 and Sep-Pak C18 cartridges for purification of 18 F-FP-(+)-DTBZ may be highly suited to automatic synthesis for routine clinical applications, as it provides excellent radiochemical purity, high yield as well as operational simplicity.
An iodine-mediated method for the synthesis of 6-alkylthio-1,3,5-triazine-2,4-diamines by the reaction of N-alkylpyridinium salts and NH4SCN in air is reported. Twenty-seven compounds were obtained under the standard conditions. Pyridinium salts work as benzyl-group transfer reagents to promote the formation of the CBn–SSCN bond and thereby the construction of the triazine skeleton. A plausible mechanism is proposed based on the experimental results and literature survey.
A4K14-citropin 1.1 is a structurally optimized derivative derived from amphibians' skin secreta peptide Citropin, which exhibits broad biological activities. However, the application of A4K14-citropin 1.1 as a cancer therapeutic is restricted by its structural flexibility. In this study, a series of all-hydrocarbon stapled peptides derivatives of A4K14-citropin 1.1 were designed and synthesized, and their chemical and biological characteristics were also investigated. Among them, A4K14-citropin 1.1-Sp1 and A4K14-citropin 1.1-Sp4 displayed improved helicity levels, greater protease stability, and increased antitumor activity compared with the original peptide, which establishes them as promising lead compounds for novel cancer therapeutics development. These results revealed the important influence of all-hydrocarbon stapling side chain on the secondary structure, hydrolase stability, and biological activity of A4K14-citropin 1.1.
Abstract Osteoporosis is an emerging health issue worldwide. Due to the decrease of bone mineral density and the deterioration of skeletal microarchitecture, osteoporosis could lead to increased bone fragility and higher fracture risk. Since lack of specific symptoms, novel serum proteomic indicators are urgently needed for the evaluation of osteoporosis. Microvesicles (MVs) are important messengers widely present in body fluids and have emerged as novel targets for the diagnosis of multiple diseases. In this study, MVs were successfully isolated from human serum and comprehensively characterized. Comparative proteomics analysis revealed differential MVs protein profiling in normal subjects, osteopenia patients, and osteoporosis patients. In total, about 200 proteins were identified and quantified from serum MVs, among which 19 proteins were upregulated (fold change >2) and five proteins were downregulated (fold change <0.5) in osteopenia group and osteoporosis group when compared with the normal group. Three protein candidates were selected for initial verification, including Vinculin, Filamin A, and Profilin 1. Profilin 1 was further pre‐validated in an independent sample set, which could differentiate osteoporosis group from osteopenia group and normal group ( p < 0.05). Our data collectively demonstrate that serum MVs proteome can be valuable indicators for the evaluation and diagnostics of bone loss disease.
Insulin-like growth factor-Ⅰ(IGF-Ⅰ) is a single-chain polypeptide with structural homolog to proinsulin.It plays an important role in regulating somatic growth in vertebrates via growth hormone.To study fish IGF-Ⅰs structure,function and its potential application in aquaculture,we cloned the insulinlike growth factor-Ⅰ cDNA from bluntnose bream (Megalobrama amblycephala).Total RNA was isolated from liver tissue.The cDNA encoding IGF-Ⅰ peptide was amplified by reverse transcription polymerase chain reaction (RT-PCR) strategy using isolated total RNA as template.The amplified cDNA fragment was inserted to vector pUC18.The cloned cDNA was sequenced and the amino acid sequence of bluntnose bream IGF-Ⅰ was predicted.The nucleotide sequence showed that the cDNA encode 161 amino acids including signal peptide and B,C,A,D,E six domains.Analysis of E domain indicates that the cloned bluntnose bream IGF-Ⅰ cDNA belongs to IGF-ⅠEa-2 subtype.
To investigate the expression and clinical significance of DNA methyltransferases (DNMT) mRNA in patients with chronic myeloid leukemia (CML).The expression levels of DNMT mRNA in mononucllear cells (MNC) of bone marrow or in peripheral blood of 93 CML patients in 3 different phases and 10 normal controls (NC) were detected by SYBR Green flurescent quatitative PCR.The relative expression levels of DNMT1 mRNA in NC, chronic phase CML (CML-CP), accelerated phase (CML-AP) and blastic phase (CML-BP) were 1.45 ± 0.22, 1.83 ± 0.63, 2.95 ± 0.87 and 3.24 ± 1.39 resectively. The expression of DNMT1 mRNA showed no statistically significant difference between CML-CP and NC (P = 0.28). The expression of DNMT1 mRNA in advanced stages (including CML-AP and CML-BP) of CML obviously increased in comparison with CML-CP and NC (P < 0.05). The expression of DNMT1 mRNA in CML-AP was not significantly different from that in CML-BP (P = 0.336). The relative expression levels of DNMT3a mRNA in NC, CML-CP, CML-AP and CML-BP groups were 1.29 ± 0.34, 1.34 ± 0.46, 2.33 ± 1.05 and 3.18 ± 1.23 resectively. And the expression levels of DNMT3a mRNA were not statistically significantly different between CML-CP and NC (P = 0.844). The results showed that the expression of DNMT3a mRNA in the advanced phase of CML significantly increased in comparison with that in CML-CP and NC (P < 0.05). Meanwhile, the expression of DNMT3a mRNA in CML-AP was not different from that in CML-BP (P = 0.304). The relative expression levels of DNMT3b mRNA in NC, CML-CP, CML-AP and CML-BP groups were 1.37 ± 0.31, 16.41 ± 22.50, 9.36 ± 5.50 and 12.17 ± 13.44 resectively. It was also found that the level of DNMT3b mRNA in CML significantly increased in comparison with NC (P < 0.05), and that the between the 3 different phase of CML was not statistically significantly different (P >0.05).The expression of DNMT mRNA increases in advanced CML as compared with normal controls and CML-CP, and the increased levels of DNMT mRNA probably correlate with disease progression in CML.
CONCLUSION:The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression.PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB.
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