Therapeutic Effects of Coccomyxagloeobotrydiformis on the Metabolic Syndrome in Rats

Background/Aims: The metabolic syndrome (MS) is a cluster of metabolic changes that carry a high risk of cardiovascular disease (CVD). A newly discovered microalga, coccomyxagloeobotrydiformis (CGD), has been reported to improve ischemic stroke and metabolism-related indicators. We observed the therapeutic effects of CGD on MS and postulated the underlying mechanism. Methods: A diet-induced MS model in rats was used to observe the therapeutic effects of CGD on MS. Blood-glucose and lipid indices were measured using enzymatic colorimetric kits. A biologic data acquisition and analysis system (BL-420F) was used to evaluate cardiac function. Expression of mitochondrial respiratory chain (MRC) enzymes was measured by immunofluorescence staining. The proteins associated with oxidative stress, apoptosis and inflammation were detected by western blotting. Results: Body weight, abdominal circumference, fasting blood glucose , blood pressure as well as serum levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol were decreased whereas serum levels of high-density lipoprotein-cholesterol was increased in CGD-treated MS rats. CGD increased left-ventricular systolic pressure, left-ventricular end-diastolic pressure, left-ventricular systolic pressure maximum rate of increase and left-ventricular diastolic pressure maximum rate of decrease in MS rats with cardiovascular complications. CGD up-regulated expression of adenosine monophosphate-activated protein kinase and peroxisome proliferator activated receptor gamma coactivator 1-alpha in the heart, adipose tissue and skeletal muscle. Expression of the MRC subunits of ATPase 6, cytochrome b and succinate dehydrogenase complex, subunit-A was increased whereas that of uncoupling protein-2 decreased in different tissues. CGD showed anti-oxidation effects by increasing expression of superoxide dismutase and decreasing that of malondialdehyde. High expression of Bcl-2 and low expression of Bax and caspase-3 supported the anti-apoptotic effect of CGD on the cardiovascular complications of MS. Conclusion: CGD has a therapeutic effect on MS and associated cardiovascular complications by eliciting mitochondrial protection and having anti-oxidation and anti-apoptosis effects. CGD could be used for MS treatment

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Prognostic significance of the epithelial-to-mesenchymal transition markers e-cadherin, vimentin and twist in bladder cancer

ObjectiveThe goal of this study was to utilize long-term patient follow-up to determine whether epithelial-to-mesenchymal transition (EMT)-related markers can predict bladder cancer patient survival and progression of disease.Materials and MethodsThis study included 121 patients with bladder cancer. Sixty-four of these patients presented with non-muscle invasive (NMI, stage T1) bladder cancer and 57 with muscle invasive (MI, stage T2, T3). The patients were diagnosed and treated between May 1998 and July 2012. The EMT markers E-cadherin, Twist, and Vimentin were detected via immunohistochemistry. Univariate and multivariate/Cox analyses were then utilized to determine whether these EMT markers could be useful prognostic markers for predicting bladder cancer patient outcomes.ResultsAnalysis of the 121 bladder cancer patients in this study revealed that the frequency of E-cadherin expression was 59.5% (72/121), Twist was 54.5% (66/121), and Vimentin was 24.8% (30/121). Twist and Vimentin were found to have statistically significant correlations with grade, recurrence, and progression but not with stage, whereas E-cadherin was associated with stage but not with the other parameters. In the univariate analysis, grade (p = 0.02) was the only significant predictor for progression-free survival (PFS). Stage, grade, and expression of E-cadherin, Vimentin and Twist were included in the multivariate analysis of predicting PFS. In this analysis, grade (p = 0.01) and Vimentin expression (p = 0.001) were found to be significant prognostic factors in predicting PFS.ConclusionsGrade and Vimentin are potential independent indicators in predicting bladder cancer progression and survival