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11.
Ennian Li Kai Wang Bei Zhang Siqi Guo Senhao Xiao Qi Pan Xiaowan Wang Weiying Chen Yunshan Wu Hesong Xu Xiangqian Kong Cheng Luo Shijie Chen Bo Liu 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1537
The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity towards other S-adenosyl-L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC50 value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour. 相似文献
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Myokine IL-15 regulates the crosstalk of co-cultured porcine skeletal muscle satellite cells and preadipocytes 总被引:1,自引:0,他引:1
Yinghui Li Fengna Li Binbin Lin Xiangfeng Kong Yulong Tang Yulong Yin 《Molecular biology reports》2014,41(11):7543-7553
The present study was carried out to preliminarily reveal the underlying mechanisms of the co-culture system between porcine muscle satellite cells (SCs) and stromal-vascular cells (SVs). The two cell types were co-cultured to assess both proliferation and differentiation. Desmin and Pref-1 immunofluorescence staining technique were taken to identify the two types of isolated cells. The expression of specific marker genes Myogenin was up-regulated in SCs (P < 0.05) and the differentiation of SCs could be promoted when co-cultured with preadipocytes compared with the single-cultured control, while expression of c/EBPβ in SVs was down-regulated (P < 0.05) and the differentiation of preadipocytes could be inhibited. Furthermore, secretion of myokine IL-15 was markedly increased, as well as its gene and protein expression levels in co-culture supernatants. However, the secretion of adipokine leptin was significantly decreased. These findings demonstrate that myokines like IL-15 could facilitate the SCs’ differentiation while inhibit the SVs differentiation, and act as an important regulator of co-culture between muscle cells and adipocytes. 相似文献
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Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells 总被引:2,自引:0,他引:2
Chen Y McMillan-Ward E Kong J Israels SJ Gibson SB 《Cell death and differentiation》2008,15(1):171-182
Autophagy is a self-digestion process that degrades intracellular structures in response to stresses leading to cell survival. When autophagy is prolonged, this could lead to cell death. Generation of reactive oxygen species (ROS) through oxidative stress causes cell death. The role of autophagy in oxidative stress-induced cell death is unknown. In this study, we report that two ROS-generating agents, hydrogen peroxide (H(2)O(2)) and 2-methoxyestradiol (2-ME), induced autophagy in the transformed cell line HEK293 and the cancer cell lines U87 and HeLa. Blocking this autophagy response using inhibitor 3-methyladenine or small interfering RNAs against autophagy genes, beclin-1, atg-5 and atg-7 inhibited H(2)O(2) or 2-ME-induced cell death. H(2)O(2) and 2-ME also induced apoptosis but blocking apoptosis using the caspase inhibitor zVAD-fmk (benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone) failed to inhibit autophagy and cell death suggesting that autophagy-induced cell death occurred independent of apoptosis. Blocking ROS production induced by H(2)O(2) or 2-ME through overexpression of manganese-superoxide dismutase or using ROS scavenger 4,5-dihydroxy-1,3-benzene disulfonic acid-disodium salt decreased autophagy and cell death. Blocking autophagy did not affect H(2)O(2)- or 2-ME-induced ROS generation, suggesting that ROS generation occurs upstream of autophagy. In contrast, H(2)O(2) or 2-ME failed to significantly increase autophagy in mouse astrocytes. Taken together, ROS induced autophagic cell death in transformed and cancer cells but failed to induce autophagic cell death in non-transformed cells. 相似文献
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SN Park SW Kong MS Park JW Lee E Cho YK Lim MH Choi HS Kim YH Chang JH Shin HS Park SH Choi JK Kook 《Journal of bacteriology》2012,194(19):5445-5446
Fusobacterium nucleatum, one of the major causative bacteria of periodontitis, is classified into five subspecies (nucleatum, polymorphum, vincentii, animalis, and fusiforme) on the basis of the several phenotypic characteristics and DNA homology. This is the first report of the draft genome sequence of F. nucleatum subsp. fusiforme ATCC 51190(T). 相似文献
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Jacques Friborg Jr. Wing-Pui Kong C. Clay Flowers Scarlett L. Flowers Yongnian Sun Kimberly E. Foreman Brian J. Nickoloff Gary J. Nabel 《Journal of virology》1998,72(12):10073-10082
The DNA sequence for Kaposi’s sarcoma-associated herpesvirus was originally detected in Kaposi’s sarcoma biopsy specimens. Since its discovery, it has been possible to detect virus in cell lines established from AIDS-associated body cavity-based B-cell lymphoma and to propagate virus from primary Kaposi’s sarcoma lesions in a human renal embryonic cell line, 293. In this study, we analyzed the infectivity of Kaposi’s sarcoma-associated herpesvirus produced from these two sources. Viral isolates from cultured cutaneous primary KS cells was transmitted to an Epstein-Barr virus-negative Burkitt’s B-lymphoma cell line, Louckes, and compared to virus induced from a body cavity-based B-cell lymphoma cell line. While propagation of body cavity-based B-cell lymphoma-derived virus was not observed in 293 cell cultures, infection with viral isolates obtained from primary Kaposi’s sarcoma lesions induced injury in 293 cells typical of herpesvirus infection and was associated with apoptotic cell death. Interestingly, transient overexpression of the Kaposi’s sarcoma-associated herpesvirus v-Bcl-2 homolog delayed the process of apoptosis and prolonged the survival of infected 293 cells. In contrast, the broad-spectrum caspase inhibitors Z-VAD-fmk and Z-DEVD-fmk failed to protect infected cell cultures, suggesting that Kaposi’s sarcoma-associated herpesvirus-induced apoptosis occurs through a Bcl-2-dependent pathway. Kaposi’s sarcoma-associated herpesvirus isolates from primary Kaposi’s sarcoma lesions and body cavity-based lymphomas therefore may differ and are likely to have distinct contributions to the pathophysiology of Kaposi’s sarcoma. 相似文献
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Yoon SY Noh HS Kim EH Kong KH 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2002,132(2):415-422
An alcohol dehydrogenase (ADH) was purified to electrophoretic homogeneity from an extremely thermophilic bacterium, Thermomicrobium roseum. The native enzyme was found to be a homo-dimer of 43-kDa subunits. The pI of the enzyme was determined to be 6.2, while its optimum pH is 10.0. The enzyme oxidized mainly primary aliphatic alcohols and exhibited high substrate specificity towards ethanol, n-propanol and crotyl alcohol. The highest reaction rate was observed when ethanol was used as substrate and the K(m) value of the enzyme for ethanol was 24.2 mM. Pyrazole notably inhibited the enzymatic activity. The enzyme had the optimal temperature of 70 degrees C and was highly stable against high temperature. 相似文献