Pathological cardiac hypertrophy is associated with nearly all forms of heart failure. It develops in response to disorders such as coronary artery disease, hypertension and myocardial infarction. Angiotensin II (Ang II) has direct effects on the myocardium and promotes hypertension. Chronic elevation of Ang II can lead to pathological cardiac hypertrophy and cardiac failure. Autophagy is an important process in the pathogenesis of cardiovascular diseases. Under physiological conditions, autophagy is an essential homeostatic mechanism to maintain the global cardiac structure function by ridding damaged cells or unwanted macromolecules and organelles. Dysregulation of autophagy may play an important role in Ang II-induced cardiac hypertrophy although conflicting reports on the effects of Ang II on autophagy and cardiac hypertrophy exist. Some studies showed that autophagy activation attenuated Ang II-induced cardiac dysfunction. Others suggested that inhibition of the Ang II induced autophagy should be protective. The discrepancies may be due to different model systems and different signaling pathway involved. Ang II-induced cardiac hypertrophy may be alleviated through regulation of autophagy. This review focuses on Ang II to highlight the molecular targets and pathways identified in the prevention and treatment of Ang II-induced pathological cardiac hypertrophy by regulating autophagy.

Sphingosine‐1‐phosphate (S1P) is an endogenous metabolite derived from ceramide as part of the sphingomyelin cycle. It is a potent molecular messenger which exerts its function both intracellularly and extracellularly. Intracellularly, S1P acts as a second messenger regulating calcium mobilization, and cellular proliferation and survival. Extracellularly, S1P acts as a ligand of the G‐protein‐coupled S1P receptors (S1PRs) and mediates a variety of physiological and pathological processes. Levels of S1P and other sphingosine metabolites are maintained in a delicate balance through the action of two enzymes, sphingosine kinase (SK) and sphingosine‐1‐phosphate lyase (SPL). Our previous studies showed that exogenously administered S1P (concentration: 1 µM) exhibited synergistic effects with chemotherapy drugs in human breast cancer MCF7 and MDA‐MB‐361 cells [1, 2]. Herein, we report other cell lines and mouse xenograf study results on the antitumor activity of S1P.

Objective: To investigate the role of zdhhc17 on embryonic development in zebrafish by loss-of-function experiments. Methods: Zdhhc17 antisense morpholino oligonucleotide was injected into embryos to block the translation. The whole mount in situ hybridyzation and RT-PCR were used to detect the abnormal development after knockdown of zdhhc17. Results: Knockdown of zdhhc17 impacted convergence and extension movements during zebrafish gastrulation. The tail of zdhhc17 morphants was curved and shorter (82/118). The expression patterns of dlx3b, ntl, myod1 and tbx6 were affected. The mRNA level of cdh1 and padh18a was obviously lower in embryos injected with zdhhc17 morpholino. Conclusion: zdhhc17 is critical for zebrafish convergence and extension movements via regulating the expression of cadherin superfamily genes cdh1 and pcdh18a and affecting cell adhesion.

Sphingosine-1-phosphate (S1P) is an important sphingolipid metabolite regulating key physiological and pathophysiological processes such as cell growth and survival and tumor angiogenesis.Significant research evidence links elevated cellular S1P concentration to cancer cell proliferation, migration and angiogenesis.Physiological levels of S1P are tightly regulated and maintained at the low nanomolar level.In cancer, S1P may exist well beyond the low nanomolar level.Recently, we reported that S1P selectively induces cell apoptosis of the breast cancer MCF7 cell line at concentrations higher than 1 µM and co-administration of 1 µM S1P significantly increased the cytotoxicity of chemotherapy drug docetaxel.In this study, we show that S1P caused minor increases in cell proliferation or apoptosis, in a concentration-dependent manner, yet co-administration of 10 µM S1P exhibited a significant synergistic effect with chemotherapy drugs docetaxel, doxorubicin and cyclophosphamide.S1P increased the cytotoxic potential of each drug by 2-fold, 3-fold, and 10-fold, respectively, against the breast cancer metastatic cell line MDA-MB-361.This synergism may suggest improved anticancer drug therapy by co-administration of exogenous S1P.

Background: The study was designed to explore the relationship between the anti-implantation activity of arnebia and the expression of Mud 1 protein in the endometrium of early pregnant mice.Study design: The aqueous extract of arnebia was administered to mice on Days 1-4 postcoitum, and the mice were sacrificed to asses the implantation rate on Day 8 postcoitum. On the night of Day 4 postcoitum and on the morning of Day 5 postcoitum, the treated mice were sacrificed to study the influence on endometrium. The extract of arnebia was administered to mice on Days 11-14 postcoitum, and the mice were sacrificed to asses abortion on Day 18 postcoitum. The reversible effect of arnebia on mice was also studied.Results: The endometrium in the experimental group exhibited morphological changes compared with that in the control group. The expression of Muc1 protein was increased with the increasing doses of arnebia, while in control group, it increased a little. The experiments of pseudopregnancy and normal mice show the identical expression of Muc1. The anti-implantation effect of arnebia was reversible.Conclusion: The arnebia may prevent embryo implantation by inhibiting the decrease of the Mud 1 protein. (C) 2011 Elsevier Inc. All rights reserved.

Sphingosine-1-phosphate (S1P) is an important regulator of cancer development and progression. Its cellular concentration is controlled predominantly by sphingosine kinase (SK) and sphingosine-1-phosphate lyase (SPL). In the current study we showed that mRNA expressions for both SK and SPL were up-regulated throughout all four disease stages in human breast cancer patients. Exogenous administration of S1P produced a bell-shaped dose response for apoptosis in normal mammary gland MCF12A cells but a sigmoid-shaped apoptotic response in breast cancer MCF7 cells. Co-administration of S1P enhanced the cytotoxicity of anticancer drug docetaxel against MCF7 cells.

Two definitions of environmental factors for the inverse Gaussian distribution are proposed here. From the second definition the upper and lower confidence limits of the inverse Gaussian environmental factor are derived by a classical method. Based on the first definition the Bayes limits of the inverse Gaussian environmental factor are also given using non-informative reference prior as well as the natural conjugate prior. An application example is provided.

Environmental factor estimation for the gamma distribution with two parameters is considered here. In the consideration of the characteristics of the gamma distribution, the definition of environmental factors for the exponential distribution and the convenience of data conversion, the definition of environmental factors for the gamma distribution is proposed. In accordance with this definition, the lower and upper confidence limits of environmental factors are derived by Classical, Bayesian and Fiducial methods. Some approximate confidence limits are also given. A practical example is provided and the results indicate that the definition, the confidence limits and their approximants are suitable.

It is explained that ξ-minimax estimators exist for the binomial family. Two ξ-minimax estimators of binomial reliability are derived whose performances and regions of superiority are discussed. Two numerical examples are presented. The estimators are admissible in the usual sense.

Cemented carbides are hard and tough materials for cutting tool, consisting of micrometer-sized carbides embedded in a ductile metal binder phase. In order to increase the performance and extend the service lifetime of the cemented carbides, graded cemented carbides have been developed. The formation of gradient zone during liquid phase sintering is a diffusion-controlled process, and knowledge of diffusivity is indispensable to understand formation mechanism, optimize technological parameters and design a new type of graded cemented carbides. In this paper, a diffusion database for multi-component C–Co–Cr–W–Ta–Ti–Nb–N cemented carbides has been developed through a combination of experiment, theoretical analysis and assessment. The diffusion database contains the atomic mobility parameters for different diffusing elements in liquid and fcc phase. The atomic mobility parameters in liquid phase are theoretically calculated by the newly modified Sutherland equation, and the atomic mobility parameters in fcc phase are optimized by the diffusivities measured in the present work and from the literature. In conjunction with the thermodynamic database for cemented carbides (CSUTDCC1: Central South University Thermodynamic Database for Cemented Carbides—version-1), the diffusion database (CSUDDCC1: Central South University Diffusion Database for Cemented Carbides—version-1) can be used to simulate the gradient sintering process. Simulations of different kinds of graded cemented carbides are presented using the databases and compared where possible against experimental data, in order to validate its accuracy.