Caffeic Acid Derivatives Inhibit the Growth of Colon Cancer: Involvement of the PI3-K/Akt and AMPK Signaling Pathways

The aberrant regulation of phosphatidylinositide 3-kinases (PI3-K)/Akt, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (m-TOR) signaling pathways in cancer has prompted significant interest in the suppression of these pathways to treat cancer. Caffeic acid (CA) has been reported to possess important anti-inflammatory actions. However, the molecular mechanisms by which CA derivatives including caffeic acid phenethyl ester (CAPE) and caffeic acid phenylpropyl ester (CAPPE), exert inhibitory effects on the proliferation of human colorectal cancer (CRC) cells have yet to be elucidated

A joint individual-based model coupling growth and mortality reveals that tree vigor is a key component of tropical forest dynamics

Tree vigor is often used as a covariate when tree mortality is predicted from tree growth in tropical forest dynamic models, but it is rarely explicitly accounted for in a coherent modeling framework. We quantify tree vigor at the individual tree level, based on the difference between expected and observed growth. The available methods to join nonlinear tree growth and mortality processes are not commonly used by forest ecologists so that we develop an inference methodology based on an MCMC approach, allowing us to sample the parameters of the growth and mortality model according to their posterior distribution using the joint model likelihood. We apply our framework to a set of data on the 20-year dynamics of a forest in Paracou, French Guiana, taking advantage of functional trait-based growth and mortality models already developed independently. Our results showed that growth and mortality are intimately linked and that the vigor estimator is an essential predictor of mortality, highlighting that trees growing more than expected have a far lower probability of dying. Our joint model methodology is sufficiently generic to be used to join two longitudinal and punctual linked processes and thus may be applied to a wide range of growth and mortality models. In the context of global changes, such joint models are urgently needed in tropical forests to analyze, and then predict, the effects of the ongoing changes on the tree dynamics in hyperdiverse tropical forests. (Résumé d'auteur

A model building exercise of mortality risk for Taiwanese women with breast cancer

Abstract Background The accurate estimation of outcome in patients with malignant disease is an essential component of the optimal treatment, decision-making and patient counseling processes. The prognosis and disease outcome of breast cancer patients can differ according to geographic and ethnic factors. To our knowledge, to date these factors have never been validated in a homogenous loco-regional patient population, with the aim of achieving accurate predictions of outcome for individual patients. To clarify this topic, we created a new comprehensive prognostic and predictive model for Taiwanese breast cancer patients based on a range of patient-related and various clinical and pathological-related variables. Methods Demographic, clinical, and pathological data were analyzed from 1 137 patients with breast cancer who underwent surgical intervention. A survival prediction model was used to allow analysis of the optimal combination of variables. Results The area under the receiver operating characteristic (ROC) curve, as applied to an independent validation data set, was used as the measure of accuracy. Results were compared by comparing the area under the ROC curve. Conclusions our model building exercise of mortality risk was able to predict disease outcome for individual patients with breast cancer. This model could represent a highly accurate prognostic tool for Taiwanese breast cancer patients.</p

Student performance assessment using clustering techniques

The application of informatics in the university system management allows managers to count with a great amount of data which, rationally treated, can offer significant help for the student programming monitoring. This research proposes the use of clustering techniques as a useful tool of management strategy to evaluate the progression of the students’ behavior by dividing the population into homogeneous groups according to their characteristics and skills. These applications can help both the teacher and the student to improve the quality of education. The selected method is the data grouping analysis by means of fuzzy logic using the Fuzzy C-means algorithm to achieve a standard indicator called Grade, through an expert system to enable segmentation.Universidad de la Costa, 2 Universidad Nacional Experimental Politécnica “Antonio José de Sucre”, Universidad Simón Bolívar, Corporación Universitaria Latinoamericana, Corporación Universitaria Minuto de Dios

Impact of Resistant Starch on Body Fat Patterning and Central Appetite Regulation

Background: Adipose tissue patterning has a major influence on the risk of developing chronic disease. Environmental influences on both body fat patterning and appetite regulation are not fully understood. This study was performed to investigate the impact of resistant starch (RS) on adipose tissue deposition and central regulation of appetite in mice. Methodology and Principle Findings: Forty mice were randomised to a diet supplemented with either the high resistant starch (HRS), or the readily digestible starch (LRS). Using 1H magnetic resonance (MR) methods, whole body adiposity, intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) were measured. Manganese-enhanced MRI (MEMRI) was used to investigate neuronal activity in hypothalamic regions involved in appetite control when fed ad libitum. At the end of the interventional period, adipocytes were isolated from epididymal adipose tissue and fasting plasma collected for hormonal and adipokine measurement. Mice on the HRS and LRS diet had similar body weights although total body adiposity, subcutaneous and visceral fat, IHCL, plasma leptin, plasma adiponectin plasma insulin/glucose ratios was significantly greater in the latter group. Adipocytes isolated from the LRS group were significantly larger and had lower insulin-stimulated glucose uptake. MEMRI data obtained from the ventromedial and paraventricular hypothalamic nuclei suggests a satiating effect of the HRS diet despite a lower energy intake. Conclusion and Significance: Dietary RS significantly impacts on adipose tissue patterning, adipocyte morphology and metabolism, glucose and insulin metabolism, as well as affecting appetite regulation, supported by changes in neuronal activity in hypothalamic appetite regulation centres which are suggestive of satiation

Measurement of CP Asymmetries and Branching Fractions in a Time-Dependent Dalitz Analysis of B^0-->(rho pi)^0 and a Constraint on the Quark Mixing Angle phi_2

We present the results of a time-dependent Dalitz plot analysis of B0 --> pi+ pi- pi0 decays based on a 414/fb data sample that contains 449 x 10^6 BB pairs. The data was collected on the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric energy e+e- collider. Combining our analysis with information on charged B decay modes, we perform a full Dalitz and isospin analysis and obtain a constraint on the quark mixing angle phi_2, 68deg. < phi_2 < 95deg. at the 68.3% confidence level for the phi_2 solution consistent with the standard model (SM). A large SM-disfavored region also remains. The branching fractions for the decay processes of B0 --> rho+-(770) pi-+ and B0 --> rho0(770) pi0 are measured to be (22.6 +- 1.1[stat.] +- 4.4 [syst.]) x 10^{-6} and (3.0 +- 0.5 [stat.] +- 0.7 [syst.]) x 10^{-6}, respectively. These are the first branching fraction measurements of the process B0 --> rho(770)pi with the lowest resonance rho(770) explicitly separated from the radial excitations.Comment: 26 pages, 12 figures, to be submitted to Phys. Rev. D; Revision to Phys. Rev. D published versio

4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells

The estrogenic chemical 4-nonylphenol (NP) is known to impair testicular devolopment and spermatogenesis in rodents. The objective of this study was to explore the effects of NP on autophagy induction and AMPK-mTOR signaling pathway in Sertoli cells (SCs), which are the “nursemaid cells” for meiosis of spermatocytes. In this study we exposed 7-week-old male rats to NP by intra-peritoneal injection at 0, 20, 50 or 100 mg/kg body weight/2 days for 20 consecutive days. Our results showed that exposure to NP dose-dependently induces the formation of autophagosomes in SCs, increases the expression of Beclin-1, the conversion of LC3-I to LC3-II and the mRNA expression of Atg3, Atg5, Atg7 and Atg12 in testis, and these effects are concomitant with the activation of AMPK, and the suppression of TSC2-mTOR-p70S6K/4EBP1 signaling cascade in testis. Furthermore, 10 µM Compound C or AMPKα1 siRNA pre-treatment effectively attenuated autophagy and reversed AMPK-mTOR-p70S6K/4EBP1 signaling in NP-treated SCs. Co-treatment with 1 mM AICAR remarkably strengthened NP-induced autophagy and mTOR inhibition in SCs. Together, these data suggest that NP stimulates Sertoli cell autophagy and inhibits mTOR-p70S6K/4EBP1 activity through AMPK activation, which is the potential mechanism responsible for the regulation of testis function and differentiation following NP exposure

Risk groups defined by Recursive Partitioning Analysis of patients with colorectal adenocarcinoma treated with colorectal resection

<p>Abstract</p> <p>Background</p> <p>To define different prognostic groups of surgical colorectal adenocarcinoma patients derived from recursive partitioning analysis (RPA).</p> <p>Methods</p> <p>Ten thousand four hundred ninety four patients with colorectal adenocarcinoma underwent colorectal resection from Taiwan Cancer Database during 2003 to 2005 were included in this study. Exclusion criteria included those patients with stage IV disease or without number information of lymph nodes. For the definition of risk groups, the method of classification and regression tree was performed. Main primary outcome was 5-year cancer-specific survival.</p> <p>Results</p> <p>We identified six prognostic factors for cancer-specific survival, resulting in seven terminal nodes. Four risk groups were defined as following: Group 1 (mild risk, 1,698 patients), Group 2 (moderate risk, 3,129 patients), Group 3 (high risk, 4,605 patients) and Group 4 (very high risk, 1,062 patients). The 5-year cancer-specific survival for Group 1, 2, 3, and 4 was 86.6%, 62.7%, 55.9%, and 36.6%, respectively (p < 0.001). Hazard ratio of death was 2.13, 5.52 and 10.56 (95% confidence interval 1.74-2.60, 4.58-6.66 and 8.66-12.9, respectively) times for Group 2, 3, and 4 as compared to Group 1. The predictive capability of these grouping was also similar in terms of overall and progression-free survival.</p> <p>Conclusion</p> <p>The use of RPA offered an alternative grouping method that could predict the survival of patients who underwent surgery for colorectal adenocarcinoma.</p

MicroRNA-335 acts as a metastasis suppressor in gastric cancer by targeting Bcl-w and specificity protein 1

Aberrant expression of miR-335 has been frequently reported in cancer studies, suggesting that there is a close correlation between miR-335 and cancer during its development, progression, metastasis and prognosis. The expression of miR-335 in gastric cancer and its effects are not known. Relative expression of miR-335 in 4 gastric cancer cell lines and in 70 gastric cancer tissues was confirmed by real-time quantitative reverse transcriptase-PCR compared with controls. Transwell cell migration and Matrigel invasion assay in vitro and metastasis formation assay in vivo were used to examine the effects of miR-335 expression on gastric cancer cell invasion and metastasis. The effect of miR-335 expression on gastric cancer cell proliferation was estimated by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Luciferase reporter assay and western blot were used to examine the potential target genes and related pathways. Gene silencing with small-interfering RNA was used to examine the effects of target genes on gastric cancer cell invasion. miR-335 was dramatically downregulated in gastric cancer cell lines than in the normal gastric cell line GES-1. Low expression of miR-335 was significantly associated with lymph-node metastasis, poor pT stage, poor pN stage and invasion of lymphatic vessels. Overexpression of miR-335 suppressed gastric cancer cell invasion and metastasis in vitro and in vivo, but has no significant effects on cell proliferation. Furthermore, miR-335 might suppress gastric cancer invasion and metastasis by targeting Bcl-w and specificity protein 1 (SP1). Taken together, our results provide evidence that miR-335 might function as a metastasis suppressor in gastric cancer by targeting SP1 directly and indirectly through the Bcl-w-induced phosphoinositide 3-kinase-Akt-Sp1 pathway. miR-335 showing altered expression at different stages of gastric cancer could be a target for gastric cancer therapies and could be further developed as a potential prognostic factor

Ultrasonographic median nerve cross-section areas measured by 8-point "inching test" for idiopathic carpal tunnel syndrome: a correlation of nerve conduction study severity and duration of clinical symptoms

<p>Abstract</p> <p>Background</p> <p>Incremental palmar stimulation of the median nerve sensory conduction at the wrist, the "inching test", provides an assessment with reference to segments proximal and distal to the entrapment. This study used high-resolution ultrasonography (US) to measure the median nerve's cross-section areas (CSAs) like the "inching test" and to correlate with the nerve conduction study (NCS) severity and duration of carpal tunnel syndrome (CTS).</p> <p>Methods</p> <p>Two hundred and twelve (212) "CTS-hands" from 135 CTS patients and 50 asymptomatic hands ("A-hands") from 25 control individuals were enrolled. The median nerve CSAs were measured at the 8-point marked as <it>i</it>4, <it>i</it>3, <it>i</it>2, <it>i</it>1, <it>w</it>, <it>o</it>1, <it>o</it>2, and <it>0</it>3 in inching test. The NCS severities were classified into six groups based on motor and sensory responses (i.e., negative, minimal, mild, moderate, severe, and extreme). Results of US studies were compared in terms of NCS severity and duration of clinical CTS symptoms.</p> <p>Results</p> <p>There was significantly larger CSA of the NCS negative group of "CTS-hands" than of "A-hands". The cut-off values of the CSAs of the NCS negative CTS group were 12.5 mm², 11.5 mm²and 10.1 mm²at the inlet, wrist crease, and outlet, respectively. Of the 212 "CTS-hands", 32 were NCS negative while 40 had minimal, 43 mild, 85 moderate, 10 severe, and two extreme NCS severities. The CSAs of "CTS-hands" positively correlated with different NCS severities and with the duration of CTS symptoms. By duration of clinical symptoms, 12 of the 212 "CTS-hands" were in the 1 month group; 82 in >1 month and ≤12 months group, and 118 in >12 months group. In "inching test", segments <it>i</it>4-<it>i</it>3 and <it>i</it>3-<it>i</it>2 were the most common "positive-site". The corresponding CSAs measured at <it>i</it>4 and <it>i</it>3, but not at <it>i</it>2, were significantly larger than those measured at points that were not "positive-site".</p> <p>Conclusions</p> <p>Using the 8-point measurement of the median nerve CSA from inlet to outlet similar to the "inching test" has positive correlations with NCS severity and duration of CTS clinical symptoms, and can provide more information on anatomic changes. Combined NCS and US studies using the 8-point measurement may have a higher positive rate than NCS alone for diagnosing CTS.</p