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41.
Jiahong Meng Chenhe Zhou Wenkan Zhang Wei Wang Bin He Bin Hu Guangyao Jiang Yangxin Wang Jianqiao Hong Sihao Li Jiamin He Shigui Yan Weiqi Yan 《Journal of cellular and molecular medicine》2019,23(10):6730-6743
Osteoclast overactivation‐induced imbalance in bone remodelling leads to pathological bone destruction, which is a characteristic of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, periprosthetic osteolysis and periodontitis. Natural compounds that suppress osteoclast formation and function have therapeutic potential for treating these diseases. Stachydrine (STA) is a bioactive alkaloid isolated from Leonurus heterophyllus Sweet and possesses antioxidant, anti‐inflammatory, anticancer and cardioprotective properties. However, its effects on osteoclast formation and function have been rarely described. In the present study, we found that STA suppressed receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclast formation and bone resorption, and reduced osteoclast‐related gene expression in vitro. Mechanistically, STA inhibited RANKL‐induced activation of NF‐κB and Akt signalling, thus suppressing nuclear factor of activated T cells c1 induction and nuclear translocation. In addition, STA alleviated bone loss and reduced osteoclast number in a murine model of LPS‐induced inflammatory bone loss. STA also inhibited the activities of NF‐κB and NFATc1 in vivo. Together, these results suggest that STA effectively inhibits osteoclastogenesis both in vitro and in vivo and therefore is a potential option for treating osteoclast‐related diseases. 相似文献
42.
Reversal of multidrug resistance by calcium channel blocker SR33557 without photoaffinity labeling of P-glycoprotein 总被引:5,自引:0,他引:5
J P Jaffrézou J M Herbert T Levade M N Gau P Chatelain G Laurent 《The Journal of biological chemistry》1991,266(29):19858-19864
The altered pharmacology of drugs in multidrug-resistant cells (decreased accumulation and retention) appears to be mediated by a high molecular weight integral membrane protein, called P-glycogprotein (P-gp). Agents known to reverse this pleiotropic drug resistance (chemosensitizers) have been shown to interact with P-gp; and as such, the inhibition of photoaffinity labeling by P-gp probes (such as [3H]azidopine) has been proposed as a basis for mass screening of chemosensitizers. In this study, we provide direct evidence that a novel calcium channel blocker (SR33557), which was 4.5 times more potent in sensitizing P388/ADR cells to doxorubicin as compared to verapamil (while inducing a similar increase in uptake and decrease in efflux of [14C]doxorubicin, did not compete for the [3H]azidopine-binding site on P-gp, whereas verapamil did. Moreover, SR33557, which is inherently photoactivable, did not photolabel P-gp, but a 65-kDa protein did appear to be an acceptor; and this binding was displaced by diltiazem and nifedipine, but not by verapamil. Finally, the implication for the participation of a sphingomyelin/sphingosine cycle (as a potential lipid second messenger system) in the chemosensitization of P388/ADR cells was investigated. 30 microM SR33557 induced a 72% inhibition in acid lysosomal sphingomyelinase activity, a 5-fold increase in sphingosine levels, and a 75% inhibition in intracellular protein kinase C activity. Although no direct link is established between these observations and P-gp activity, further studies on a possible sphingosine-mediated regulation of P-gp may yield information on the involvement of this second messenger system in the action of SR33557. 相似文献
43.
G Gau 《BMJ (Clinical research ed.)》1977,1(6076):1580-1581
The necropsy diagnoses in 78 stillborn and young infants have been compared with the clinical diagnoses in an attempt to justify post-morten examination in this age group. Clinical diagnosis was confirmed in over 88% of cases but unexpected changes in diagnosis were made in six cases, which indicates that selection is of no value. 相似文献
44.
Parasites in grizzly bears from the central Canadian Arctic. 总被引:1,自引:0,他引:1
Standardized flotation techniques were used to survey 56 grizzly bear (Ursus arctos) fecal samples for parasites. The samples were collected during the spring and autumn of 1995 and 1996 in the central Arctic of the Northwest Territories (Canada). Parasites of the genera Nematodirus, gastrointestinal coccidia, and an unidentified first stage protostrongylid larva are reported for the first time from grizzly bear feces in North America. Parasites of the genera Diphyllobothrium and Baylisascaris also were collected. Prevalence of gastrointestinal parasites were significantly different between the spring and autumn seasons (31% and 58% respectively). Thus, we provide evidence supporting the theory that bears void gastrointestinal parasites before hibernation. 相似文献
45.
Xiao Jun Liu Bao Yao Yingyin Guo Zifeng Jia Haiyan Kong Lingrang Zhang Aimin Ma Wujun Ni Zhongfu Xu Shengbao Lu Fei Jiao Yuannian Yang Wuyun Lin Xuelei Sun Silong Lu Zefu Gao Lifeng Zhao Guangyao Cao Shuanghe Chen Qian Zhang Kunpu Wang Mengcheng Wang Meng Hu Zhaorong Guo Weilong Li Guoqiang Ma Xin Li Junming Han Fangpu Fu Xiangdong Ma Zhengqiang Wang Daowen Zhang Xueyong Ling Hong-Qing Xia Guangmin Tong Yiping Liu Zhiyong He Zhonghu Jia Jizeng Chong Kang 《中国科学:生命科学英文版》2022,65(9):1718-1775
Science China Life Sciences - Bread wheat (Triticum aestivum L.) is a major crop that feeds 40% of the world’s population. Over the past several decades, advances in genomics have led to... 相似文献
46.
Ryu MJ Liu Y Zhong X Du J Peterson N Kong G Li H Wang J Salamat S Chang Q Zhang J 《The Journal of biological chemistry》2012,287(27):22948-22958
Previous studies suggest that up-regulation of Ras signaling in neurons promotes gliosis and astrocytoma formation in a cell nonautonomous manner. However, the underlying mechanisms remain unknown. To address this question, we generated compound mice (LSL Kras G12D/+;CamKII-Cre) that express oncogenic Kras from its endogenous locus in postmitotic neurons after birth. These mice developed progressive gliosis, which is associated with hyperactivation of Ras signaling pathways. Microarray analysis identified S100A8 and S100A9 as two secreted molecules that are significantly overexpressed in mutant cortices. In contrast to their usual predominant expression in myeloid cells, we found that overexpression of S100A8 and S100A9 in the mutant cortex is primarily in neurons. This neuronal expression pattern is associated with increased infiltration of microglia in mutant cortex. Moreover, purified S100A8-S100A9 but not S100A8 or S100A9 alone promotes growth of primary astrocytes in vitro through both TLR4 and receptor of advanced glycation end product receptors. In summary, our results identify overexpression of S100A8-S100A9 in neurons as an early step in oncogenic Kras-induced gliosis. These molecules expressed in nonhematopoietic cells may be involved in tumorigenesis at a stage much earlier than what has been reported previously. 相似文献
47.
Wang C Sheng G Lu J Xie L Bai S Wang Y Liu Y 《Molecular and cellular biochemistry》2012,359(1-2):125-133
NF-κB p65 is found constitutively active in acute monocytic leukemia, and has been considered an important factor for poor prognosis. Therefore, develop specifically target p65 inhibitors will be substantial interest. Until now, although several p65 inhibitors are currently in preclinical and clinical development, none of them are targeting. In this study, siRNA targeting p65 was introduced into the acute monocytic leukemia cell line THP-1 and THP-1 xenograft tumors in nude mice, and then, we measured p65 mRNA and protein levels by real-time RT-PCR and Western blotting, and levels of related protein cyclin D1, Bc1-2, and SMRT by Western blotting. We also investigated the cell cycle and apoptosis via FCM, and cell proliferation by Cell Counting Kit-8 assay. We found that p65 siRNA could effectively reduce the p65 mRNA and protein expression, arrest cells in G0/G1 phase, inhibit the proliferation and increase the apoptosis of THP-1 cells, and intratumoral injection of p65 siRNA could suppress tumor growth in nude mice. We also found that when down regulation of p65, the expression of cyclin D1 and Bc1-2 decreased, and the expression of SMRT increased in vitro and vivo. All these findings suggest that NF-κB p65 maybe an attractive candidate for the therapeutic targeting of acute monocytic leukemia. 相似文献
48.
An N-sulfonylated beta-amino alcohol (R,S,S,R)-9 with four stereogenic centers is prepared. The titanium complex of 9 is an effective catalyst to induce excellent enantioselectivities for diethylzinc addition to aromatic aldehydes with ee values up to 99%. The feature of doubling the quantity of Ti(O-i-Pr)4 required relative to the catalytic system of the Ti complex of bidentate N-sulfonylated beta-amino alcohols suggests that the two N-sulfonylated beta-amino alcohol moieties in 9 behave as two independent bidentate ligands in the catalytic system. The results obtained using ligand 15 having one N-sulfonylated beta-amino alcohol blocked support the argument of two independent active bidentate moieties in 9. 相似文献
49.
Incomplete combustion of field crop residues results in the production of char, a material rich in charcoal-type substances.
Consequently, char is an effective adsorbent of organic compounds and when incorporated into soil may adsorb soil-applied
pesticides, thereby altering their susceptibility to biodegradation. We investigated the relative importance of char, soil
pH and initial substrate concentration in biodegradation of pesticides in soils by measuring the biodegradation of benzonitrile
in soil as a function of soil char content (0% and 1% by weight), initial benzonitrile concentration (0.1, 1.06, and 10.2 mg l−1) and soil pH (5.2, 6.9 and 8.5). Preliminary experiments revealed that wheat straw char had a much greater benzonitrile sorption
capacity than did soil to which the char was added. The extent of benzonitrile degradation decreased as initial benzonitrile
concentration increased in both buffer solution and soil slurry. In contrast, the degradation increased as initial benzonitrile
concentration increased in char-amended slurry. In un-amended soil slurry, the benzonitrile degradation was lower at pH 5.2
than at pH 6.9 or 8.5, but in char-amended soil slurry the degradation was not affected by pH, again presumably due to adsorption
of benzonitrile by the char. Adsorption by soil char appears to be more important than either initial substrate concentration
or soil pH in controlling benzonitrile degradation in char-amended soil slurry. The presence of crop residue-derived chars
may alter pesticide degradation patterns normally observed in soils and thus significantly affect their environmental fate. 相似文献
50.
Jeschke P Harder A Etzel W Gau W Göhrt A Benet-Buchholz J Thielking G 《Bioorganic & medicinal chemistry letters》2005,15(9):2375-2379
The racemic 7-substituted 3,4a-dimethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2-b]pyridine-6,8(7H)-diones represent novel tricyclic compounds with strong in vivo efficacy against the parasitic nematode Haemonchus contortus Rudolphi in sheep. Here we report on the synthesis of tricyclic endo-2,3-dihydro[3,2-b]pyridine-type cycloadducts and describe the separation of the racemic 3,4a-dimethyl-7-ethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2]pyridine-6,8(7H)-dione into the enantiomers by HPLC. The absolute configuration of the most anthelmintically active (4aS,5aS,8aS,8bR)-enantiomer was determined by single crystal X-ray analysis using its stable (4aS,5aS,8aS,8bR)-enantiomer-CuCl2 (2:1)-complex. 相似文献