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81.
One novel lavandulyl flavanone (=2,3-dihydro-2-phenyl-4H-1-benzopyran-4-one) with an unusual 5,2',4',6'-tetrahydroxy substitution, calycinigin A (1), was isolated from the stems of Hypericum calycinum L. (Hypericaceae). The structure was elucidated on the basis of 1D- and 2D-NMR analysis, as well as mass spectrometry (LR-EI- and HR-EI-MS) and circular dichroism. Three known lavandulyl flavanones with 5,7,2',4',6'-pentahydroxy substitution, i.e., 2-4, were also isolated. Chemosystematically, this is the first report on the occurrence of prenylated flavanones in the family Hypericaceae. Reduction of cell viability by all compounds was evaluated in a MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay using HeLa cells. Compound 1 showed moderate activity with an IC?? value of 9.7±1.8?μM, whereas compounds 2-4 were less active exhibiting IC?? values of 11.6±0.9, 19.3±1.5, and 40.7±2.4?μM, respectively. The antioxidant activity was evaluated by an ORAC (Oxygen Radical Absorbance Capacity) assay, and calycinigin A (1) was again the most active compound with a Trolox equivalent of 2.3±0.2. None of the compounds was able to reduce the TNF-α induced ICAM-1 expression in vitro using human microvascular endothelial cells (HMEC-1). 相似文献
82.
Myint AM 《The FEBS journal》2012,279(8):1375-1385
Psychiatric disorders are documented to be associated with a mild pro-inflammatory state. Pro-inflammatory mediators could activate the tryptophan breakdown and kynurenine pathway with a shift toward the neurotoxic arm where excitotoxic N-methyl-D-aspartate receptor agonist quinolinic acid is formed. An unbalanced metabolism in terms of neuroprotective and neurotoxic effects, such as reduced kynurenic acid to kynurenine ratio, has been demonstrated in the major psychiatric disorders such as unipolar depression, bipolar manic-depressive disorder and schizophrenia, and in drug-induced neuropsychiatric side effects such as interferon-α treated patients. The changes in serum or plasma are shown to be associated with central changes such as in the cerebrospinal fluid and certain brain areas. While currently available antidepressants and mood stabilizers could not efficiently improve these neurochemical changes within the same period that could induce clinical improvement, some antipsychotic treatments could reverse certain metabolic imbalances. Some of these changes were tested also in animal models. In this review the role of this unbalanced kynurenine metabolism through interactions with other neurochemicals is discussed as a major contributing pathophysiological mechanism in psychiatric disorders. Moreover, the biomarker role of kynurenine metabolites and future therapeutic opportunities are also discussed. 相似文献
83.
Yimon Aye Marcus J. C. Long JoAnne Stubbe 《The Journal of biological chemistry》2012,287(42):35768-35778
Triapine® (3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP)) is a drug in Phase II trials. One of its established cellular targets is the β2 subunit of ribonucleotide reductase that requires a diferric-tyrosyl-radical [(FeIII2-Y·)(FeIII2)] cofactor for de novo DNA biosynthesis. Several mechanisms for 3-AP inhibition of β2 have been proposed; one involves direct iron chelation from β2, whereas a second involves Y· destruction by reactive oxygen species formed in situ in the presence of O2 and reductant by Fe(II)-(3-AP). Inactivation of β2 can thus arise from cofactor destruction by loss of iron or Y·. In vitro kinetic data on the rates of 55Fe and Y· loss from [(55FeIII2-Y·)(55FeIII2)]-β2 under aerobic and anaerobic conditions reveal that Y· loss alone is sufficient for rapid β2 inactivation. OxyblotTM and mass spectrometric analyses of trypsin-digested inhibited β2, and lack of Y· loss from H2O2 and O2˙̄ treatment together preclude reactive oxygen species involvement in Y· loss. Three mammalian cell lines treated with 5 μm 3-AP reveal Y· loss and β2 inactivation within 30-min of 3-AP-exposure, analyzed by whole-cell EPR and lysate assays, respectively. Selective degradation of apo- over [(FeIII2-Y·)(FeIII2)]-β2 in lysates, similar iron-content in β2 immunoprecipitated from 3-AP-treated and untreated [55Fe]-prelabeled cells, and prolonged (12 h) stability of the inhibited β2 are most consistent with Y· loss being the predominant mode of inhibition, with β2 remaining iron-loaded and stable. A model consistent with in vitro and cell-based biochemical studies is presented in which Fe(II)-(3-AP), which can be cycled with reductant, directly reduces Y· of the [(FeIII2-Y·)(FeIII2)] cofactor of β2. 相似文献
84.
85.
Sestak K McNeal MM Choi A Cole MJ Ramesh G Alvarez X Aye PP Bohm RP Mohamadzadeh M Ward RL 《Journal of virology》2004,78(19):10258-10264
The appearance of virus-specific CD4(+) and/or CD8(+) T lymphocytes in peripheral blood of captive juvenile rhesus macaques (Macaca mulatta) was observed following rotavirus infection. These cell-mediated immune responses were measured following experimental or natural infection after rotavirus was isolated from stool specimens of asymptomatic animals. The virus isolated was a new strain of simian rotavirus that we named TUCH (for Tulane University and Cincinnati Children's Hospital). Restimulation of peripheral T lymphocytes by inactivated double- or triple-layered TUCH rotavirus particles containing either VP6 or VP4 and VP7 on their respective surfaces resulted in increased quantities of interleukin-6 (IL-6) and IL-12 in cell culture supernatants. Recall responses to rotavirus by CD4(+) and CD8(+) T lymphocytes were associated with accumulation of intracellular IL-6 and gamma interferon. Antigen presentation of TUCH rotavirus to lymphocytes was mediated via differentiated cultures of monocyte-derived dendritic (HLA-DR(+)) cells. This is the first report demonstrating cell-mediated immune responses to rotavirus in nonhuman primates. Further exploration of rhesus macaques in vaccine trials with human rotavirus vaccine candidates is the major objective of future studies. 相似文献
86.
87.
Constitutive activation of MAP kinase kinase (MEK1) is critical and sufficient for the activation of MMP-2 总被引:3,自引:0,他引:3
Kurata H Thant AA Matsuo S Senga T Okazaki K Hotta N Hamaguchi M 《Experimental cell research》2000,254(1):180-188
We investigated the role of MEK1 signaling in MMP-2 activation by use of constitutive active/dominant negative forms of MEK1 and MEK1-specific inhibitor. We found that cell transformation with active forms of MEK1 dramatically increased secretion and proteolytic activation of MMP-2 and subsequently stimulated invasiveness of cells. Contrary, expression of dominant negative form of MEK1 in v-src-transformed cells or in Con A-activated cells resulted in the suppression of the augmented secretion and proteolytic activation of MMP-2. In addition, treatment of v-src-transformed cells with PD98059, a MEK1-specific inhibitor, strongly suppressed the secretion and activation of MMP-2, whereas treatment with wortmannin, a PI3 kinase inhibitor, showed no clear effect on MMP-2 secretion. Taken together, these results strongly suggest that MEK-MAP kinase signaling, but not PI3 kinase signaling, plays a critical role in the activation of MMP-2 secretion and, subsequently, in the invasiveness of v-src-transformed cells. 相似文献
88.
Saitoh M Aye NN Komori S Nakazawa T Hashimoto K 《Molecular and cellular biochemistry》2000,205(1-2):133-140
HNS-32 (N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3, 8-dimethylazulene-1-carboxamidine: CAS 186086-10-2) is a newly synthesized compound, and possesses antiarrhythmic properties with vasodilator action in dog hearts. The aim of this study was to investigate the dose-dependent effects of HNS-32 on ischemia- and/or reperfusion-induced ventricular arrhythmias in anesthetized rats in vivo and compared with those of mexiletine. Saline or drugs were administered intravenously 5 min prior to coronary artery occlusion. On the ischemia-induced ventricular arrhythmias, HNS-32 showed dose-dependent reduction of total number of premature ventricular complexes (PVC) from 2091 ± 225 to 656 ± 116 and 286 ± 69 beats/30 min (p < 0.05), the ventricular tachycardia (VT) duration from 183 ± 33 to 28 ± 9 and 4 ± 2 sec (p < 0.05), the incidence of VT from 100 to 90 (n.s.) and 40% (p < 0.05), and the incidence of ventricular fibrillation (VF) from 50 to 0 and 0% (p < 0.05) with 3 and 5 mg/kg, respectively. Mexiletine also reduced these parameters to 936 ± 159 beats/30 min (p < 0.05), 39 ± 22 sec (p < 0.05), 90% (n.s.) and 10% (n.s.), respectively. HNS-32 completely suppressed the late reperfusion-induced arrhythmias, however mexiletine did not affect them. On the early reperfusion-induced ventricular arrhythmias, HNS-32 showed dose-dependent reduction of VT duration from 126 ± 34 to 37 ± 12 and 3 ± 2 sec (p < 0.05), incidence of VT from 100 to 90 (n.s.) and 40% (p < 0.05), incidence of VF from 100 to 10 and 0% (p < 0.05), and mortality rate from 90 to 0 and 0% (p < 0.05), with 3 and 5 mg/kg, respectively. Mexiletine also reduced these parameters to 16 ± 9 sec (p < 0.05), 80 (n.s.), 50 (p < 0.05), and 10% (p < 0.05), respectively. HNS-32 significantly reduced the heart rate in a dose-dependent manner, from 399 ± 14 to 350 ± 8 and 299 ± 10 beats/min (p < 0.05) with 3 and 5 mg/kg, respectively. The antiarrhythmic effects of HNS-32 were more potent than that of the similar dose of mexiletine against occlusion-induced and reperfusion-induced arrhythmias in in vivo rats. 相似文献
89.
The mutualistic association between ants and hemipterans is often facultative and can be affected by the availability of other food sources. In the present study we tested whether the tending behavior of the big-headed ant, Pheidole megacephala (Fabricius), had a negative impact on the pink pineapple mealybug, Dysmicoccus brevipes (Cockerell), when alternative food sources: (1) sugar solution, (2) purified water + mealworms and (3) sugar solution + mealworms versus with purified water (control) were provided to the ant colonies. We found that the frequency of ant tending on D. brevipes decreased when ants were provided with alternative food sources. However, we did not see any aggressive behaviors and predation of ants on D. brevipes. Also, the survival of D. brevipes was not different among food condition treatments. These results suggest that the decreased tending frequency of ants can lead to the decline in ant protection service to mealybugs. 相似文献
90.
Aye T. Win Yuto Machida Yoshihiro Miyamoto Shigeto Dobata Kazuki Tsuji 《Journal of Ethology》2018,36(3):277-282
We investigated colony-level foraging activities of Diacamma sp., a queenless ponerine ant, in the field. Our aim was to elucidate the presence of any pattern in foraging activity in field colonies in relation to: (1) circadian rhythm, (2) physical environmental conditions such as extreme temperatures, (3) seasonality, and (4) short-term foraging efficiency (i.e. the success ratio in obtaining food per foraging trip). Colony-level foraging activity tended to be diurnal throughout the year, as more foraging trips were observed in the daytime. Although temperature had no linear effect on overall foraging activity, lower temperature precluded foraging at night. Overall, foraging was more frequent at times of day when foraging efficiency was high, but this relationship was weak and varied seasonally. Interestingly, we found that hourly foraging efficiency and hourly foraging activity were negatively correlated in autumn, the season when the average foraging efficiency peaked, whereas they were positively correlated in winter and spring. 相似文献