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Preparation and Evaluation of 99mTc‐labeled anti‐CD11b Antibody Targeting Inflammatory Microenvironment for Colon Cancer Imaging 
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下载免费PDF全文 Dengfeng Cheng Weihong Zou Xiao Li Yan Xiu Hui Tan Hongcheng Shi Xiangdong Yang 《Chemical biology & drug design》2015,85(6):696-701
CD11b, an active constituent of innate immune response highly expressed in myeloid‐derived suppressor cells (MDSCs), can be used as a marker of inflammatory microenvironment, particularly in tumor tissues. In this research, we aimed to fabricate a 99mTc‐labeled anti‐CD11b antibody as a probe for CD11b+ myeloid cells in colon cancer imaging with single‐photon emission computed tomography (SPECT). In situ murine colon tumor model was established in histidine decarboxylase knockout (Hdc?/?) mice by chemicals induction. 99mTc‐labeled anti‐CD11b was obtained with labeling yields of over 30% and radiochemical purity of over 95%. Micro‐SPECT/CT scans were performed at 6 h post injection to investigate biodistributions and targeting of the probe. In situ colonic neoplasma as small as 3 mm diameters was clearly identified by imaging; after dissection of the animal, anti‐CD11b immunofluorescence staining was performed to identify infiltration of CD11b+ MDSCs in microenvironment of colonic neoplasms. In addition, the images displayed intense signal from bone marrow and spleen, which indicated the origin and migration of CD11b+ MDSCs in vivo, and these results were further proved by flow cytometry analysis. Therefore, 99mTc‐labeled anti‐CD11b SPECT displayed the potential to facilitate the diagnosis of colon tumor in very early stage via detection of inflammatory microenvironment. 相似文献
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Daphnetin inhibits TNF‐α and VEGF‐induced angiogenesis through inhibition of the IKKs/IκBα/NF‐κB,Src/FAK/ERK1/2 and Akt signalling pathways 下载免费PDF全文
下载免费PDF全文 Abhishek Kumar Priyashree Sunita Shivesh Jha Shakti Prasad Pattanayak 《Clinical and experimental pharmacology & physiology》2016,43(10):939-950
Coumarins, identified as plant secondary metabolites possess diverse biological activities including anti‐angiogenic properties. Daphnetin (DAP), a plant derived dihydroxylated derivative of coumarin has shown significant pharmacological properties such as anticancer, anti‐arthritic and anti‐inflammatory. The present study was performed to investigate the anti‐angiogenic potential of DAP, focusing on the mechanism of action. The in vivo anti‐angiogenic potential of DAP was evaluated by vascular endothelial growth factor (VEGF)‐induced rat aortic ring (RAR) assay and chick chorioallantoic membrane (CAM) assay. For in vitro evaluation, wounding migration, transwell invasion, tube formation and apoptosis assays were performed on VEGF (8 ng/mL)‐induced human umbilical vein endothelial cells (HUVECs). The cellular mechanism of DAP was examined on TNFα (10 ng/mL) and VEGF‐induced HUVECs by extracting the mRNA and protein levels using RT‐qPCR and western blotting. Our data demonstrated that DAP inhibited the in vivo angiogenesis in the RAR and CAM assay. DAP also inhibited the different steps of angiogenesis, such as migration, invasion, and tube formation in HUVECs. DAP inhibited nuclear factor‐κB signalling together including TNF‐α induced IκBα degradation; phosphorylation of IκB kinase (IKKα/β) and translocation of the NF‐κB‐p65 protein. Furthermore, western blotting revealed that DAP significantly down‐regulated the VEGF‐induced signalling such as c‐Src, FAK, ERK1/2 and the related phosphorylation of protein kinase B (Akt) and VEGFR2 expressions. DAP reduced the elevated mRNA expression of iNOS, MMP2 and also, induced apoptosis in VEGF‐stimulated HUVECs by the caspase‐3 dependent pathway. Taken together, this study reveals that DAP may have novel prospective as a new multi‐targeted medication for the anti‐angiogenesis and cancer therapy. 相似文献
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Noha I. Ziedan Rania Hamdy Alessandra Cavaliere Malamati Kourti Filippo Prencipe Andrea Brancale Arwyn T. Jones Andrew D. Westwell 《Chemical biology & drug design》2017,90(1):147-155
A new series of oxadiazoles were designed to act as inhibitors of the anti‐apoptotic Bcl‐2 protein. Virtual screening led to the discovery of new hits that interact with Bcl‐2 at the BH3 binding pocket. Further study of the structure–activity relationship of the most active compound of the first series, compound 1 , led to the discovery of a novel oxadiazole analogue, compound 16j , that was a more potent small‐molecule inhibitor of Bcl‐2. 16j had good in vitro inhibitory activity with submicromolar IC50 values in a metastatic human breast cancer cell line (MDA‐MB‐231) and a human cervical cancer cell line (HeLa). The antitumour effect of 16j is concomitant with its ability to bind to Bcl‐2 protein as shown by an enzyme‐linked immunosorbent assay (IC50 = 4.27 μm ). Compound 16j has a great potential to develop into highly active anticancer agent. 相似文献
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Attalla Farag El‐kott Mohammed Ali Al‐kahtani Ali A. Shati 《Clinical and experimental pharmacology & physiology》2019,46(10):944-954
Autophagy promotes cell survival or induces apoptosis in cancer cells. While SIRT1 and AMPK induce autophagy in both normal and cancer cells, Akt and mTOR can inhibit it. Calycosin, a methoxyisoflavone, protects against several types of solid tumours including colorectal cancer. However, the mechanisms behind the antitumour effect of Calycosin remain largely unknown. This study investigates if autophagy mediates the anti‐tumourigenesis effect afforded by Calycosin and examines if this effect involves activation of SIRT1 and/or AMPK. Human colorectal (HT29) carcinoma cells were cultured under normal conditions with Calycosin (50 μmol/L) in the presence or absence of chloroquine (10 μmol/L), EX‐527 (100 nmol/L, SIRT1 inhibitor), or IGF‐1 (100 ng/mL, Akt/mTOR activator) for 48 hours. Calycosin inhibited cell growth, proliferation and invasion and increased protein levels of Beclin‐1 and LC3II, markers of autophagy. It significantly increased protein levels of cleaved caspase‐3, Bax, and SIRT1, and activity of AMPK and reduced those of Bcl‐2. These effects were parallel with concomitant reduction in protein levels p‐src, integrin‐β1 and Cyclin‐D1 and activities of Akt and mTOR. Inhibition of autophagy by CQ reversed all these effects except cell invasion. Interestingly, co‐incubating the cells with either EX‐527 or IGF‐1 completely prevented Calycosin‐induced autophagy and all other associated effects and increased cell invasion. Also, blockade of SIRT‐1 prevented the activation of AMPK, Akt, and mTOR, suggesting it to be an upstream regulator of these markers. In conclusion, Calycosin stimulates CRC cell apoptosis and inhibits their invasion by acting as SIRT1 activator which induces activation of AMPK‐induced inhibition of Akt/mTOR axis. 相似文献
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《Econometrics Journal》2018,21(3):298-315
Inferring underlying cooperative and competitive strategies from human behaviour in repeated games is important for accurately characterizing human behaviour and understanding how people reason strategically. Finite automata, a bounded model of computation, have been extensively used to compactly represent strategies for these games and are a standard tool in game theoretic analyses. However, inference over these strategies in repeated games is challenging since the number of possible strategies grows exponentially with the number of repetitions yet behavioural data are often sparse and noisy. As a result, previous approaches start by specifying a finite hypothesis space of automata that does not allow for flexibility. This limitation hinders the discovery of novel strategies that may be used by humans but are not anticipated a priori by current theory. Here we present a new probabilistic model for strategy inference in repeated games by exploiting non‐parametric Bayesian modelling. With simulated data, we show that the model is effective at inferring the true strategy rapidly and from limited data, which leads to accurate predictions of future behaviour. When applied to experimental data of human behaviour in a repeated prisoner's dilemma, we uncover strategies of varying complexity and diversity. 相似文献
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Aussara Panya Petlada Yongpitakwattana Prapaphan Budchart Nunghathai Sawasdee Sucheewin Krobthong Atchara Paemanee Sittiruk Roytrakul Siriluk Rattanabunyong Kiattawee Choowongkomon Pa‐thai Yenchitsomanus 《Chemical biology & drug design》2019,93(2):100-109
The therapeutic activities of food‐derived bioactive proteins and peptides are attracting increased attention within the research community. Medicinal plants used in traditional medicines are an excellent source of bioactive proteins and peptides, especially those traditionally prepared by water extraction for use as tea or food supplement. In this study, novel bioactive peptides were isolated from enzymatic digests of 33 Thai medicinal plants. The inhibitory activity of each against dengue virus (DENV) infection was investigated. Of 33 plants, peptides from Acacia catechu extract demonstrated the most pronounced anti‐DENV activity. Half maximal inhibitory concentration of 0.18 μg/ml effectively inhibited DENV foci formation. Treatment with 1.25 μg/ml crude peptide extract could reduce virus production less than 100‐fold with no observable cell toxicity. Peptide sequences were determined by high‐performance liquid chromatography and liquid chromatography–tandem mass spectrometry. Two bioactive peptides isolated from Acacia catechu inhibited DENV foci formation >90% at the concentration of 50 μM; therefore, they are recommended for further investigation as antiviral peptides against DENV infection. 相似文献
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Discovery of a Potent 9‐Deazaxanthine‐based Agent for the Treatment of Obesity‐Related Non‐alcoholic Fatty Liver Disease 下载免费PDF全文
下载免费PDF全文 Jinying Chen Liang Ma Li Huang Caifeng Xie Heying Pei Linhong He Suhong Fu Lijuan Chen 《Chemical biology & drug design》2015,86(1):66-79
A series of deazaxanthine‐based derivatives were rationally prepared and evaluated. 8g exhibited the most potent glucose‐lowering effect on HepG2 cell line and modulated adiponectin and leptin expression in 3T3‐L1 adipocytes. Oral administration of 8g at 25 mg/kg/day for 4 weeks manifested therapeutic effects on high‐fat diet‐induced non‐alcoholic fatty liver disease (NAFLD) by decreasing the weights of the body, liver, and fat. 8g also modulated the serum levels of fasting glucose and adiponectin, triglycerides, low‐density lipoprotein‐cholesterol, and alanine aminotransferase, as well as the hepatic concentrations of triglycerides, total cholesterol. Moreover, 8g significantly decreased steatosis and blocked the increase of adipocytes and the size of adipose tissues from NAFLD. In the DIO mice model, 8g ameliorated the obesity‐related symptoms and normalized serum biomarkers. 相似文献
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Yulei Cui Lei Jiang Yun Shao Lijuan Mei Yanduo Tao 《The Journal of pharmacy and pharmacology》2019,71(2):240-250
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《Econometrics Journal》2018,21(3):264-276
A popular approach to factor‐augmented panel regressions is the common correlated effects (CCE) estimator of Pesaran (2006). In fact, the approach is so popular that it has given rise to a separate CCE literature. A common assumption in this literature is that the common factors are stationary, which would seem to rule out many empirically relevant cases. Moreover, deterministic factors are typically treated as known, which raises the issue of model misspecification. In the current paper, we show how the conditions placed on the factors in CCE can be made much more general than was previously thought possible. In fact, save for some mild regulatory moment conditions, the factors are essentially unrestricted. One implication of this result is that there is no need to discriminate between deterministic and stochastic factors, but that one can instead treat them all as unknown. This is very convenient for practitioners, because it means that under certain conditions they are spared the problem of having to decide which deterministic terms to include in the model. 相似文献