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21.
Sun X Phan TN Jung SH Kim SY Cho JU Lee H Woo SH Park TK Yang BS 《The Journal of pharmacology and experimental therapeutics》2012,340(3):510-519
Wound healing generally induces an inflammatory response associated with tissue fibrosis in which activated macrophage and myofibroblast cells are primarily involved. Although this is known to be the underlying mechanism for scarring and various fibrotic pathologies, no effective intervention is currently available. We identified (3-(2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-ylamino)phenol (LCB 03-0110), a thienopyridine derivative, as a potent inhibitor of discoidin domain receptor family tyrosine kinases and discovered that this compound strongly inhibits several tyrosine kinases, including the c-Src family, spleen tyrosine kinase, Bruton's tyrosine kinase, and vascular endothelial growth factor receptor 2, which are important for immune cell signaling and inflammatory reactions. LCB 03-0110 suppressed the proliferation and migration of primary dermal fibroblasts induced by transforming growth factor β1 and type I collagen, and this result correlated with the inhibition ability of the compound against enhanced expression of α-smooth muscle actin and activation of Akt1 and focal adhesion kinase. In J774A.1 macrophage cells activated by lipopolysaccharide LCB 03-0110 inhibited cell migration and nitric oxide, inducible nitric-oxide synthase, cyclooxygenase 2, and tumor necrosis factor-α synthesis. LCB 03-0110 applied topically to full excisional wounds on rabbit ears suppressed the accumulation of myofibroblast and macrophage cells in the healing wound and reduced hypertrophic scar formation after wound closing, without delaying the wound closing process. Taken together, the pharmacological activities of LCB 03-0110 suggest that it could be an effective agent for suppressing fibroinflammation by simultaneously targeting activated fibroblasts and macrophages. 相似文献
22.
Chan Daniel Kam Yin Chan Luke Kar Man Kuang Ye Min Le Mai Nhat Vi Celler Branko 《European journal of ageing》2022,19(3):309-323
European Journal of Ageing - Fall prevention and management of behavioural and psychological symptoms of dementia (BPSD) in long-term care (LTC) facility is a major challenge. The objective of this... 相似文献
23.
Tan Phat Nguyen Tien Dung Le Nhat Minh Phan Trong Dat Bui Dinh Tri Mai 《Journal of Asian natural products research》2016,18(6):542-549
From the leaves of Schefflera sessiliflora De P. V., two new triterpene saponins including one oleanane-type saponin, named scheffleraside C (1) and one lupane-type saponin scheffleraside D (2), together with six known triterpene saponins (3–8), were isolated by various chromatography methods. Among them, 3 was found for the first time from natural sources, while 6–8 were isolated for the first time from the genus Schefflera. Their structures were elucidated by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments, and comparison of their NMR data with previously reported data. Their α-glucosidase inhibition and cytotoxic activity against MCF-7 human breast cancer cell lines were evaluated. The isolates (1, 3–5, 8) showed stronger α-glucosidase inhibitory activity (IC50 = 5.99–76.58 μM) than the standard drug acarbose (IC50 = 214.50 μM). At the concentration of 100 μg/ml, the isolates (1, 2) showed appreciable cytotoxic activity (67.92, 63.83%, respectively). 相似文献
24.
Although the mechanisms underlying prion propagation and infectivity are now well established, the processes accounting for prion toxicity and pathogenesis have remained mysterious. These processes are of enormous clinical relevance as they hold the key to identification of new molecular targets for therapeutic intervention. In this review, we will discuss two broad areas of investigation relevant to understanding prion neurotoxicity. The first is the use of in vitro experimental systems that model key events in prion pathogenesis. In this context, we will describe a hippocampal neuronal culture system we developed that reproduces the earliest pathological alterations in synaptic morphology and function in response to PrPSc. This system has allowed us to define a core synaptotoxic signaling pathway involving the activation of NMDA and AMPA receptors, stimulation of p38 MAPK phosphorylation and collapse of the actin cytoskeleton in dendritic spines. The second area concerns a striking and unexpected phenomenon in which certain structural manipulations of the PrPC molecule itself, including introduction of N‐terminal deletion mutations or binding of antibodies to C‐terminal epitopes, unleash powerful toxic effects in cultured cells and transgenic mice. We will describe our studies of this phenomenon, which led to the recognition that it is related to the induction of large, abnormal ionic currents by the structurally altered PrP molecules. Our results suggest a model in which the flexible N‐terminal domain of PrPC serves as a toxic effector which is regulated by intramolecular interactions with the globular C‐terminal domain. Taken together, these two areas of study have provided important clues to underlying cellular and molecular mechanisms of prion neurotoxicity. Nevertheless, much remains to be done on this next frontier of prion science. 相似文献
25.
Kristina C. Skåtun Tobias Kaufmann Christine L. Brandt Nhat Trung Doan Dag Alnæs Siren Tønnesen Guido Biele Anja Vaskinn Ingrid Melle Ingrid Agartz Ole A. Andreassen Lars T. Westlye 《Brain imaging and behavior》2018,12(3):640-652
The thalamus is a highly connected subcortical structure that relays and integrates sensory and cortical information, which is critical for coherent and accurate perceptual awareness and cognition. Thalamic dysfunction is a classical finding in schizophrenia (SZ), and resting-state functional MRI has implicated somatomotor and frontal lobe thalamic dysconnectivity. However, it remains unclear whether these findings generalize to different psychotic disorders, are confined to specific thalamic sub-regions, and how they relate to structural thalamic alterations. Within-thalamic and thalamo-cortical functional connectivity was assessed using resting-state functional MRI data obtained from patients with SZ (n = 96), bipolar disorder (BD, n = 57), and healthy controls (HC, n = 280). Further, we used thalamic sub-regions as seeds to investigate specific cortical connectivity patterns, and performed structural analyses of thalamic volume and shape. Results showed reduced within-thalamic connectivity and thalamo-frontoparietal coupling in SZ and increased thalamo-somatomotor connectivity in BD. One thalamic sub-region showed increased sensory connectivity in SZ and eight sub-regions showed reductions with frontal and posterior areas. Reduced gray matter and shape abnormalities were found in frontal-projecting regions in both SZ and BD, but did not seem to explain reduced functional connectivity. Aberrant thalamo-cortical connectivity patterns in SZ and BD supports the notion of the thalamus as a key structure in the functional connectome across the psychosis spectrum, and the frontal and somatomotor anatomical distribution is in line with the characteristic cognitive and perceptual symptoms in psychotic disorders. 相似文献
26.
27.
Texture analysis of ultrahigh field T2*‐weighted MR images of the brain: Application to Huntington's disease
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28.
静松灵[2-(2,4-二甲基苯胺基)-4,5-二氢噻唑,XT]是国内合成的麻醉物,经ip给药后,从大鼠尿中分离、纯化、鉴定了四个代谢产物。MB1即XT原形;MB3及MA2互为异构体,分别为2位、4位甲基氧化为羧基的产物;MA1则4位甲基氧化为羧基,二氢噻唑环中41位亚甲基氧化为羰基。初步实验表明:代谢产物MB3,MA2,MA1的药效与毒性均远低于原形药,大鼠与小鼠对XT的转化机制相近,但也存在种属的差异。 相似文献
29.
Kieu Anh Thi Nguyen Thu Tuyet Nguyen Dong Vinh Nguyen Giang Chau Ngo Cam Nhat Nguyen Kentaro Yamada Kazuko Noguchi Kamruddin Ahmed Hanh Duc Hoang Akira Nishizono 《Tropical Medicine and Health》2015,43(2):111-116
Rapid and easy determination of protective neutralization antibody (NAb) against rabies in the field is very important for an early and effective response to rabies in both animal and human health sectors. The rapid neutralizing antibody detection test (RAPINA), first developed in 2009 and then improved in 2012, is a quick test allowing detection of 0.5 IU/ml antibodies in human and animal sera or plasma. This study aimed to assess the RAPINA test by comparison with rapid focus fluorescence inhibition test (RFFIT), using 214 sera of vaccinated and unvaccinated professional dog butchers, laboratory workers and rabies patients in Vietnam. The sensitivity, specificity, false negative rate, false positive rate and concordance of the RAPINA test as compared to RFFIT were 100%, 98.34%, 0%, 1.66% and 98.6%, respectively. The positive predictive value and negative predictive value were 91.7% and 100%, respectively when RAPINA test was used. With its remarkable sensitivity, specificity and easy implementation, RAPINA test can be used for rapid determination of NAb in the field. 相似文献
30.
YuJian Zhang Laiman Xiang Raffit Hassan Chang H Paik Jorge A Carrasquillo Beom-Su Jang Nhat Le Mitchell Ho Ira Pastan 《Clinical cancer research》2006,12(15):4695-4701
PURPOSE: To investigate the combined antitumor activity in mice of immunotoxin SS1P and Taxol. Methods: Immunodeficient mice were implanted with A431/K5 tumors expressing mesothelin. Established tumors were treated i.v. with immunotoxin SS1P alone, i.p. with Taxol alone, or with the two agents together. SS1P was radiolabeled with (111)In and used to study the effect of Taxol on its uptake by A431/K5 tumors. RESULTS: Using doses at which either agent alone caused stabilization of tumor growth, the combination was synergistic causing long-lasting complete remissions in many animals. In contrast, synergy was not observed when the same cells were treated with these agents in vitro. Tumor uptake of (111)In-SS1P was not affected by treatment with Taxol. CONCLUSION: The combination of Taxol and SS1P exerts a synergistic antitumor effect in animals but not in cell culture. This effect is not secondary to increased tumor uptake of the immunotoxin. Synergy could be due to improved immunotoxin distribution within the tumor or could involve factors released by other cell types in the tumors. 相似文献