Deoxycholic acid induces the overexpression of intestinal mucin, MUC2, via NF-kB signaling pathway in human esophageal adenocarcinoma cells

<p>Abstract</p> <p>Background</p> <p>Mucin alterations are a common feature of esophageal neoplasia, and alterations in MUC2 mucin have been associated with tumor progression in the esophagus. Bile acids have been linked to esophageal adenocarcinoma and mucin secretion, but their effects on mucin gene expression in human esophageal adenocarcinoma cells is unknown.</p> <p>Methods</p> <p>Human esophageal adenocarcinoma cells were treated 18 hours with 50–300 μM deoxycholic acid, chenodeoxycholic acid, or taurocholic acid. MUC2 transcription was assayed using a MUC2 promoter reporter luciferase construct and MUC2 protein was assayed by Western blot analysis. Transcription Nuclear factor-κB activity was measured using a Nuclear factor-κB reporter construct and confirmed by Western blot analysis for Nuclear factor-κB p65.</p> <p>Results</p> <p>MUC2 transcription and MUC2 protein expression were increased four to five fold by bile acids in a time and dose-dependent manner with no effect on cell viability. Nuclear factor-κB activity was also increased. Treatment with the putative chemopreventive agent aspirin, which decreased Nuclear factor-κB activity, also decreased MUC2 transcription. Nuclear factor-κB p65 siRNA decreased MUC2 transcription, confirming the significance of Nuclear factor-κB in MUC2 induction by deoxycholic acid. Calphostin C, a specific inhibitor of protein kinase C (PKC), greatly decreased bile acid induced MUC2 transcription and Nuclear factor-κB activity, whereas inhibitors of MAP kinase had no effect.</p> <p>Conclusion</p> <p>Deoxycholic acid induced MUC2 overexpression in human esophageal adenocarcinoma cells by activation of Nuclear factor-κB transcription through a process involving PKC-dependent but not PKA, independent of activation of MAP kinase.</p

Bi-level programming approach to optimal strategy for vendor-managed inventory problems under random demand

We present an extension of vendor-managed inventory (VMI) problems by considering advertising and pricing policies. Unlike the results available in the literature, the demand is supposed to depend on the retail price and advertising investment policies of the manufacturer and retailers, and is a random variable. Thus, the constructed optimization model for VMI supply chain management is a stochastic bi-level programming problem, where the manufacturer is the upper level decision-maker and the retailers are the lower-level ones. By the expectation method, we first convert the stochastic model into a deterministic mathematical program with complementarity constraints (MPCC). Then, using the partially smoothing technique, the MPCC is transformed into a series of standard smooth optimization subproblems. An algorithm based on gradient information is developed to solve the original model. A sensitivity analysis has been employed to reveal the managerial implications of the constructed model and algorithm: (1) the market parameters of the model generate significant effects on the decision-making of the manufacturer and the retailers, (2) in the VMI mode, much attention should be paid to the holding and shortage costs in the decision-making. doi:10.1017/S144618111700038

MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGF , and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed

Exploring the Dynamical Behavior of Information Diffusion in D2D Communication Environment

This paper is dedicated to exploring the dynamical behavior of information diffusion in the Device-to-Device (D2D) communication environment for information security, so as to study how to accelerate the dissemination of beneficial information and curb the spread of malicious information. A mathematical model of information diffusion considering the combined impact of user awareness and social tie between users is proposed. The equilibrium of the model and its stability are fully analyzed. Very importantly, there is a unique (viral) equilibrium that is globally asymptotically stable without any preconditions. This means that the spread of malicious information in the D2D communication environment cannot be completely eliminated whatever measures are taken, but its diffusion scale can be controlled by adjusting the value of the equilibrium, and then the goal of pursuing the best control effect at the minimum cost can be achieved. In the same way, the dissemination scale of beneficial information can be expanded. Finally, the obtained main theoretical results are illustrated by some examples, and some suggestions are also given