Robust nonlinear control of blood glucose in diabetic patients subject to model uncertainties.

Recent advances in the artificial pancreas system provide an emerging treatment option for type 1 diabetes. The performance of the blood glucose regulation directly relies on the accuracy of the glucose-insulin modeling. Sorenson model involves the behavior of different organs and offers precise representation. However, the high complexity of such a model makes the controller design procedure a hard task. Therefore, the high-order nonlinear Sorensen model as a popular high-fidelity physiological model is opted in this paper to analyze the glucose-insulin interactions in great detail, and a new robust nonlinear approach to regulate the blood glucose concentration (BGC) in Type-I diabetic patients is proposed. Inspiring the backstepping technique, for designing an acceptable controller, the model is divided into three main subsystems such that in each subsystem, the virtual control input laws are obtained using both Lyapunov stability and input-to-state theorems. Since the measurement of the parameters in the glucose-insulin system is not accurate, parametric uncertainties are defined in the investigated model. Furthermore, owing to the fact that the only measurable state variable is blood glucose, the estimation of inaccessible state variables is an important issue that is properly considered by the unscented Kalman filter (UKF) estimator. The suggested approach is compared to H∞, robust H∞, and linear parameter-varying control approaches. The comparison results on 500 simulated patients imply a remarkable superiority of the proposed controller approach to the compared methods in terms of the BGC tracking and the algorithm robustness in the presence of food intake disturbance patterns.

Wogonin and neobaicalein from Scutellaria litwinowii roots are apoptotic for HeLa cells

Chemical investigation on the CH2Cl2 fraction of the Scutellaria litwinowii Bornm. & Sint., Lamiaceace, root extract for the first time resulted in the isolation of wogonin, and neobaicalein. These compounds were evaluated for their cytotoxicity towards HeLa cell lines and lymphocytes. Meanwhile, the role of apoptosis was explored in this toxicity. The cells were cultured in RPMI medium and incubated with different concentrations of isolated flavonoids. Cell viability was quantified by MTS assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1peak). Wogonin, and neobaicalein inhibited the growth of malignant cells in a dose-dependent manner. The IC50 values of 46.62 and 79.34 µM were, respectively, found for neobaicalein and wogonin against HeLa cells after 48 h of treatment. Neobaicalein induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in neobaicalein toxicity. Neobaicalein exerts cytotoxic and pro-apoptotic effects in HeLa cell lines and could be considered as a potential chemotherapeutic agent in cancer treatment.