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Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.
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Longgu is the fossil of ancient mammals which was used as a common kind of mineral medicine. Longgu is always used to treat neurological diseases. Currently, the quality standard of Longgu is incomplete. Moreover, because of the non-renewable nature of the resource and the increase of national protection of fossils, the clinical application of Longgu is facing a series of problems. As the discovery of the ingredient and the development of forging technology researchers launched to search the substitutes of Longgu. The article summarizes the usage and the study of Longgu, in order that we can discuss the modern usage and substitutability of Longgu.
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Objective:To investigate the influencing factors of coronary slow flow (CSF) in relevant patients.Methods:A total of 1 530 patients received coronary angiography (CAG) in our hospital from 2008-01 to 2010-09 were retrospectively studied.According to corrected TIMI frame counts,2 groups were established:CSF group,n=139 patients without obvious coronary artery stenosis but with CSF and Control group,n=232 patients without obvious coronary artery stenosis and with normal coronary blood flow.Basic clinical condition,risk factors and routine laboratory tests were compared between 2 groups;the influencing factors of CSF were evaluated by multivariate Logistic regression analysis.Results:① The following parameters were different between 2 groups:age,gender,histories of smoking and diabetes;red blood cells (RBC),hemoglobin,mean hemoglobin concentration,hematocrit (HCT),mean RBC volume,RBC distribution width;neutrophils,monocytes,basophilic granulocyte,the ratios of lymphocytes/monocytes (LMR),neutrophils/monocytes (NMR),neutrophils/lymphocytes (NLR) and platelet/lymphocytes (PLR);glutamic oxalacetic transaminase,creatine kinase and total bile acid,P＜0.05.② Correlation analysis showed that RBC (r=0.191,P＜0.01),hemoglobin (r=0.184,P＜0.01),neutrophils (r=0.218,P＜0.01),mean hemoglobin concentration (r=0.151,P＜0.01),mean RBC volume (r=-0.138,P＜0.01),total bile acid (r=-0.172,P＜0.01),NLR (r=0.231,P＜0.01),LMR (r=-0.157,P＜0.01) and NMR (r=0.121,P＜0.01)were related to 3-branch mean flow frame.③ Multivariate Logistic regression analysis indicated that total bile acid (partial regression coefficient=-0.102,P＜0.01),LMR (partial regression coefficient =-0.381,P＜0.01) and NMR (partial regression coefficient =0.489,P＜0.01) were the independent influencing factors of coronary slow flow.Conclusion:Total bile acids,LMR and NMR were the influencing factors of coronary slow flow in relevant patients.
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Objective:To investigate the influencing factors of coronary slow flow (CSF) in relevant patients.Methods:A total of 1 530 patients received coronary angiography (CAG) in our hospital from 2008-01 to 2010-09 were retrospectively studied.According to corrected TIMI frame counts,2 groups were established:CSF group,n=139 patients without obvious coronary artery stenosis but with CSF and Control group,n=232 patients without obvious coronary artery stenosis and with normal coronary blood flow.Basic clinical condition,risk factors and routine laboratory tests were compared between 2 groups;the influencing factors of CSF were evaluated by multivariate Logistic regression analysis.Results:① The following parameters were different between 2 groups:age,gender,histories of smoking and diabetes;red blood cells (RBC),hemoglobin,mean hemoglobin concentration,hematocrit (HCT),mean RBC volume,RBC distribution width;neutrophils,monocytes,basophilic granulocyte,the ratios of lymphocytes/monocytes (LMR),neutrophils/monocytes (NMR),neutrophils/lymphocytes (NLR) and platelet/lymphocytes (PLR);glutamic oxalacetic transaminase,creatine kinase and total bile acid,P＜0.05.② Correlation analysis showed that RBC (r=0.191,P＜0.01),hemoglobin (r=0.184,P＜0.01),neutrophils (r=0.218,P＜0.01),mean hemoglobin concentration (r=0.151,P＜0.01),mean RBC volume (r=-0.138,P＜0.01),total bile acid (r=-0.172,P＜0.01),NLR (r=0.231,P＜0.01),LMR (r=-0.157,P＜0.01) and NMR (r=0.121,P＜0.01)were related to 3-branch mean flow frame.③ Multivariate Logistic regression analysis indicated that total bile acid (partial regression coefficient=-0.102,P＜0.01),LMR (partial regression coefficient =-0.381,P＜0.01) and NMR (partial regression coefficient =0.489,P＜0.01) were the independent influencing factors of coronary slow flow.Conclusion:Total bile acids,LMR and NMR were the influencing factors of coronary slow flow in relevant patients.
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<p><b>OBJECTIVE</b>To establish the chromatography-efficacy relation method for analyzing the anti-inflammatory activity of Qizhi Weitong particles, in order to lay a foundation for quality control and pharmacodynamic evaluation of traditional Chinese medicine compounds.</p><p><b>METHOD</b>On the basis of a full-time multi-wavelength fusion fingerprint of Qizhi Weitong particles, the latin hypercube sampling was used to divide six herbs in Qizhi Weitong particles into groups of different proportions to determine their inhibition ratios of TNF-alpha, IL-6 and NO released by LPS-induced RAW264. 7 cells. Pharmaeodynamic data and chemical information of HPLC fingerprints of each group were analyzed with the gray correlation method to get the anti-inflammatory effect of each chromatographic peak, and then fitted with BP neural network to establish the chromatography-efficacy relation.</p><p><b>RESULT</b>There were 25 peaks closely related to the anti-inflammatory activity. With the 25 peaks as input items, the 3-BP network was adopted to establish the neural network model for anti-inflammatory effect of Qizhi Weitong particles.</p><p><b>CONCLUSION</b>With an error of less than 7%, the model could better fit with the complicated non-linear relation of the compound, and applied in studying the chromatography-efficacy relation. In this study on the chromatography-efficacy relation, a new method is established to evaluate the anti-inflammatory activity of Qizhi Weitong particles. It is of practical significance as an effective approach for controlling quality and exploring the material basis for efficacy of traditional Chinese medicine compounds.</p>