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1.
《Bioorganic & medicinal chemistry letters》2014,24(24):5666-5670
Thirty-one 4-oxoquinoline-3-carboxamides derivatives were synthesized and evaluated for their anti-fibrotic activities by the inhibition of TGF-β1-induced total collagen accumulation and anti-inflammatory activities by the inhibition of LPS-stimulated TNF-α production. Among them, three compounds (10a, 10l and 11g) exhibited potent inhibitory effects on both TGF-β1-induced total collagen accumulation and LPS-stimulated TNF-α production. Furthermore, oral administrations of 10l at a dose of 20 mg/kg/day for 4 weeks effectively alleviated lung inflammation and injury, and decreased lung collagen accumulation in bleomycin-induced pulmonary fibrosis model. Histopathological evaluation of lung tissue confirmed 10l as a potential, orally active agent for the treatment of pulmonary fibrosis. 相似文献
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《Bioorganic & medicinal chemistry》2016,24(21):5052-5060
Targeting the interaction between G-Protein Coupled Receptor, CXCR4, and its natural ligand CXCL12 is a leading strategy to mitigate cancer metastasis and reduce inflammation. Several pyridine-based compounds modeled after known small molecule CXCR4 antagonists, AMD3100 and WZ811, were synthesized. Nine hit compounds were identified. These compounds showed lower binding concentrations than AMD3100 (1000 nM) and six of the nine compounds had an effective concentration (EC) less than or equal to WZ811 (10 nM). Two of the hit compounds (2g and 2w) inhibited invasion of metastatic cells at a higher rate than AMD3100 (62%). Compounds 2g and 2w also inhibit inflammation in the same range as WZ811 in the paw edema test at 40% reduction in inflammation. These preliminary results are the promising foundation of a new class of pyridine-based CXCR4 antagonists. 相似文献
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摘要 目的:探讨肺癌合并肺部感染患者病原菌分布、耐药性分析及血清炎性因子检测的临床意义。方法:选取我院于2018年6月~2020年3月期间收治的肺癌合并肺部感染患者90例为感染组,选取同期我院收治的肺癌未合并肺部感染患者100例为肺癌组,选取同期于我院进行体检的健康志愿者60例为对照组,对肺癌合并肺部感染患者的感染病原菌类型进行总结分析,分析常见病原菌药敏试验结果,统计病原菌耐药率。对比三组受试者的炎性因子水平。结果:90例肺癌合并肺部感染患者的送检痰液标本共检出100株病原菌,100株病原菌中以革兰阴性菌为主,其次为革兰阳性菌、真菌,分别占比63.00%、22.00%、15.00%。肺炎克雷伯菌、鲍氏不动杆菌、铜绿假单胞菌对亚胺培南的耐药率较低,对氨苄西林、甲氨苄啶的耐药率均较高。凝固酶阴性葡萄球菌、金黄色葡萄球菌对万古霉素的耐药率较高,对左氧氟沙星的耐药率较低。白色念珠菌、热带念珠菌对两性霉素B、氟康唑、酮康唑、伊曲康唑的耐药率均较低。感染组、肺癌组的血清白介素-6(IL-6)、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)水平均高于对照组,且感染组以上指标水平高于肺癌组(P<0.05)。结论:肺癌合并肺部感染患者体内病原菌种类繁多,对常见抗菌药物的耐药性存在差异,且患者体内存在较强的炎性反应,临床应根据药敏结果合理应用抗菌药物 。 相似文献
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《Cell calcium》2019
Cardiorespiratory disease, which includes systemic arterial hypertension, restenosis, atherosclerosis, pulmonary arterial hypertension, asthma, and chronic obstructive pulmonary disease (COPD) are highly prevalent and devastating diseases with limited therapeutic modalities. A common pathophysiological theme to these diseases is cellular remodeling, which is contributed by changes in expression and activation of ion channels critical for either excitability or growth. Calcium (Ca2+) signaling and specifically ORAI Ca2+ channels have emerged as significant regulators of smooth muscle, endothelial, epithelial, platelet, and immune cell remodeling. This review details the dysregulation of ORAI in cardiorespiratory diseases, and how this dysregulation of ORAI contributes to cellular remodeling. 相似文献
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The dispersion of inhaled microparticles in the pulmonary acinus of the lungs is often attributed to the complex interplay between convective mixing, due to irreversible flows, and intrinsic particle motion (i.e. gravity and diffusion). However, the role of each mechanism, the exact nature of such interplay between them and their relative importance still remain unclear. To gain insight into these dispersive mechanisms, we track liquid-suspended microparticles and extract their effective diffusivities inside an anatomically-inspired microfluidic acinar model. Such results are then compared to experiments and numerical simulations in a straight channel. While alveoli of the proximal acinar generations exhibit convective mixing characteristics that lead to irreversible particle trajectories, this local effect is overshadowed by a more dominant dispersion mechanism across the ductal branching network that arises from small but significant streamline crossing due to intrinsic diffusional motion in the presence of high velocity gradients. We anticipate that for true airborne particles, which exhibit much higher intrinsic motion, streamline crossing would be even more significant. 相似文献
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Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources. 相似文献
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Paul W. Brandt-Rauf Matthew R. Pincus Robert P. Carty Jack Lubowsky Matthew Avitable John Carucci Randall B. Murphy 《Journal of Protein Chemistry》1989,8(1):149-157
The binding of cancer cells to the basement membrane glycoprotein laminin appears to be a critical step in the metastatic process. This binding can be inhibited competitively by a specific pentapeptide sequence (Tyr-Ile-Gly-Ser-Arg) of the laminin B1 chain, and this peptide can prevent metastasis formationin vivo. However, other similar pentapeptide sequences (e.g., Tyr-Ile-Gly-Ser-Glu) have been found to be much less active in metastasis inhibition, raising the possibility that such amino acid substitutions produce structural changes responsible for altering binding to the laminin receptor. In this study, conformational energy analysis has been used to determine the three-dimensional structures of these peptides. The results indicate that the substitution of Glu for the terminal Arg produces a significant conformational change in the peptide backbone at the middle Gly residue. These results have important implications for the design of drugs that may be useful in preventing metastasis formation and tumor spread. 相似文献