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排序方式: 共有150条查询结果,搜索用时 375 毫秒
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Galanski ME Erker T Handler N Lemmens-Gruber R Kamyar M Studenik CR 《Bioorganic & medicinal chemistry》2006,14(3):826-836
A series of new nonpeptide vasopressin antagonists with a 6-ethyl-thieno[2,3-b][1,4]thiazine or 6-benzyl-thieno[2,3-b][1,4]thiazine skeleton and structural modifications of the aryl side chain were synthesized in this study. The effects on guinea pig heart and smooth muscle preparations were investigated. In the presence of AVP the compounds showed an antagonistic effect. The compounds did not change spontaneous rate in right atria and exerted a slight but not significant negative inotropic effect in papillary muscles. The relaxing effect on vascular smooth muscle and terminal ileum was far more pronounced. Generally the relaxing effect on terminal ilea was more potent maybe due to difference in V1a receptor density. Our results demonstrate that compounds with an ethyl group in position six on the thienothiazine ring (14, 16, 18 and 22) exerted the most potent relaxing activity in terminal ilea, whereas compounds with a phenyl ring in position six reduced this effect. 相似文献
44.
Rafiee P Shi Y Pritchard KA Ogawa H Eis AL Komorowski RA Fitzpatrick CM Tweddell JS Litwin SB Mussatto K Jaquiss RD Baker JE 《The Journal of biological chemistry》2003,278(44):43636-43644
Many infants who undergo cardiac surgery have a congenital cyanotic defect where the heart is chronically perfused with hypoxemic blood. Infant hearts adapt to chronic hypoxemia by activation of intracellular protein kinase signal transduction pathways. However, the involvement of heat shock protein 70 in adaptation to chronic hypoxemia and its role in protein kinase signaling pathways is unknown. We determined expression of message and subcellular protein distribution for inducible (Hsp70i) and constitutive heat shock protein 70 (Hsc70) in chronically hypoxic and normoxic infant human and rabbit hearts and their relationship to protein kinases. In chronically hypoxic human and rabbit hearts message levels for Hsp70i were elevated 4- to 5-fold compared with normoxic hearts, Hsp70i protein was redistributed from the particulate to the cytosolic fraction. In normoxic infants Hsp70i protein was distributed almost equally between the cytosolic and particulate fractions. Hsc70 message and subcellular distribution of Hsc70 protein were unaffected by chronic hypoxia. We then determined if protein kinases influence Hsp70i protein subcellular distribution. In rabbit hearts SB203580 and chelerythrine reduced Hsp70i message levels, whereas SB203580, chelerythrine, and curcumin reversed the subcellular redistribution of Hsp70i protein caused by chronic hypoxia, with no effect in normoxic hearts, indicating regulation of Hsp70i message and subcellular distribution of Hsp70i protein in chronically hypoxic rabbit hearts is influenced by protein kinase C and mitogen-activated protein kinases, specifically p38 MAPK and JNK. We conclude the Hsp70 signal transduction pathway plays an important role in adaptation of infant human and rabbit hearts to chronic hypoxemia. 相似文献
45.
Wagdy M. Eldehna Mohammed S. Taghour Tarfah Al-Warhi Alessio Nocentini Mostafa M. Elbadawi Hazem A. Mahdy Mohamed A. Abdelrahman Ohoud J. Alotaibi Nada Aljaeed Diaaeldin M. Elimam Kamyar Afarinkia Hatem A. Abdel-Aziz Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):531
Different 2,4-thiazolidinedione-tethered coumarins 5a–b, 10a–n and 11a–d were synthesised and evaluated for their inhibitory action against the cancer-associated hCAs IX and XII, as well as the physiologically dominant hCAs I and II to explore their selectivity. Un-substituted phenyl-bearing coumarins 10a, 10 h, and 2-thienyl/furyl-bearing coumarins 11a–c exhibited the best hCA IX (KIs between 0.48 and 0.93 µM) and hCA XII (KIs between 0.44 and 1.1 µM) inhibitory actions. Interestingly, none of the coumarins had any inhibitory effect on the off-target hCA I and II isoforms. The sub-micromolar compounds from the biochemical assay, coumarins 10a, 10 h and 11a–c, were assessed in an in vitro antiproliferative assay, and then the most potent antiproliferative agent 11a was tested to explore its impact on the cell cycle phases and apoptosis in MCF-7 breast cancer cells to provide more insights into the anticancer activity of these compounds. 相似文献
46.
Zohreh Abdolvahabi Mitra Nourbakhsh Saman Hosseinkhani Zahra Hesari Mohsen Alipour Meisam Jafarzadeh Seyedeh Sara Ghorbanhosseini Parvaneh Seiri Zeynab Yousefi Sahar yarahmadi Pegah Golpour 《Journal of cellular biochemistry》2019,120(6):9356-9368
Downregulation of microRNA-590-3p (miR-590-3p) is a frequently occurring, nonphysiological event which is observed in several human cancers, especially breast cancer. However, the significance of miR-590-3p still remain unclear in the progression of this disease. This study explored the role of miR-590-3p in apoptosis of breast cancer cells. Gene expression of miR-590-3p, Sirtuin-1 (SIRT1), Bcl-2 associated X protein (BAX), and p21 was evaluated with real-time polymerase chain reaction (PCR) and SIRT1 protein expression was assessed by Western blot analysis in breast cancer cell lines. Bioinformatics analysis and luciferase reporter assay were used to evaluate targeting of SIRT1 messenger RNA (mRNA) by miR-590-3p. Cells were transfected with miR-590-3p mimic and inhibitor and their effects on the expression and activity of SIRT1 were evaluated. The effects of miR-590-3p upregulation on the acetylation of p53 as well as cell viability and apoptosis were assessed by Western blot analysis, WST-1 assay, and flow cytometry, respectively. miR-590-3p expression was considerably downregulated in breast cancer cells which was accompanied by upregulation of SIRT1 expression. SIRT1 was recognized as a direct target for miR-590-3p in breast cancer cells and its protein expression and activity was dramatically inhibited by the miR-590-3p. In addition, there was an increase in p53 and its acetylated form that ultimately led to upregulation of BAX and p21 expression, suppression of cell survival, and considerable induction of apoptosis in breast cancer cells. These findings suggest that miR-590-3p exerts tumor-suppressing effects through targeting SIRT1 in breast cancer cells, which makes it a potential therapeutic target for developing more efficient treatments for breast cancer. 相似文献
47.
Advances in wearable technology allow for the objective assessment of motor performance in both in-home and in-clinic environments and were used to explore motor impairments in Parkinson’s disease (PD). The aims of this study were to: 1) assess differences between in-clinic and in-home gait speed, and sit-to-stand and stand-to-sit duration in PD patients (in comparison with healthy controls); and 2) determine the objective physical activity measures, including gait, postural balance, instrumented Timed-up-and-go (iTUG), and in-home spontaneous physical activity (SPA), with the highest correlation with subjective/semi-objective measures, including health survey, fall history (fallers vs. non-fallers), fear of falling, pain, Unified Parkinson''s Disease Rating Scale, and PD stage (Hoehn and Yahr). Objective assessments of motor performance were made by measuring physical activities in the same sample of PD patients (n = 15, Age: 71.2±6.3 years) and age-matched healthy controls (n = 35, Age: 71.9±3.8 years). The association between in-clinic and in-home parameters, and between objective parameters and subjective/semi-objective evaluations in the PD group was assessed using linear regression-analysis of variance models and reported as Pearson correlations (R). Both in-home SPA and in-clinic assessments demonstrated strong discriminatory power in detecting impaired motor function in PD. However, mean effect size (0.94±0.37) for in-home measures was smaller compared to in-clinic assessments (1.30±0.34) for parameters that were significantly different between PD and healthy groups. No significant correlation was observed between identical in-clinic and in-home parameters in the PD group (R = 0.10–0.25; p>0.40), while the healthy showed stronger correlation in gait speed, sit-to-stand duration, and stand-to-sit duration (R = 0.36–0.56; p<0.03). This suggests a better correlation between supervised and unsupervised motor function assessments in healthy controls compared to PD group. In the PD group, parameters related to velocity and range-of-motion of lower extremity within gait assessment (R = 0.58–0.84), and turning duration and velocity within iTUG test (R = 0.62–0.77) demonstrated strong correlations with PD stage (p<0.01). 相似文献
48.
Anne Kathrin Müller-Rischart Anna Pilsl Patrick Beaudette Maria Patra Kamyar Hadian Maria Funke Regina Peis Alexandra Deinlein Carolin Schweimer Peer-Hendrik Kuhn Stefan F. Lichtenthaler Elisa Motori Silvana Hrelia Wolfgang Wurst Dietrich Trümbach Thomas Langer Daniel Krappmann Gunnar Dittmar Konstanze F. Winklhofer 《Molecular cell》2013,49(5):908-921
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49.
Fahimeh Mirakhori Bahman Zeynali Azita Parvaneh Tafreshi Ameneh Shirmohammadian 《Molecular reproduction and development》2013,80(4):286-296
Lithium chloride (LiCl) is a drug used to treat bipolar disorder, but has side effects in the female reproductive system. Although lithium is known to decrease folliculogenesis and induce follicular atresia in rodent ovaries, its cellular and molecular effects in the ovary have not yet been addressed. To investigate these effects, 23‐day‐old immature female rats were injected with 10 IU pregnant mare serum gonadotropin (PMSG), followed by injections of 250 mg/kg LiCl every 12 hr for four doses. Ovaries were removed 40 and 48 hr after PMSG administration and prepared for histology, immunohistochemistry, Western blotting, and DNA laddering analysis. Our results showed that in the ovaries of LiCl‐treated rats, few antral but more atretic follicles were present compared to those of the control rats. The induction of atresia by LiCl was further confirmed by the presence of DNA fragmentation, accompanied by a reduced level of 17β‐estradiol in the serum. At the cellular level, lithium significantly decreased the number of proliferating cell nuclear antigen (PCNA)‐positive cells and conversely increased the number of TUNEL‐positive cells in the granulosa layer of the antral follicles. At the molecular level, lithium increased the level of phosphorylated glycogen synthase kinase‐3β, and unexpectedly decreased the expression of active (stabilized) β‐catenin. Altogether, our results indicate that lithium disrupts the balance between proliferation and apoptosis in granulosa cells, leading to follicular atresia possibly through the reduction in both the stabilized β‐catenin and 17β‐estradiol synthesis. Mol. Reprod. Dev. 80: 286–296, 2013. © 2013 Wiley Periodicals, Inc. 相似文献