In vitro and in vivo antitumor effects of acetylshikonin isolated from Arnebia euchroma (Royle) Johnst (Ruanzicao) cell suspension cultures

<p>Abstract</p> <p>Background</p> <p>Shikonin derivatives have cytotoxic and antitumor effects. This study aims to investigate the antitumor effects of acetylshikonin isolated from a Chinese medicinal herb <it>Arnebia euchroma (Royle) Johnst</it>.</p> <p>Methods</p> <p>The 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the <it>in vitro </it>antitumor effects of acetylshikonin on human lung adenocarcinoma cell line A549, human hepatocellular carcinoma cell line Bel-7402, human breast adenocarcinoma cell line MCF-7 and mouse Lewis lung carcinoma (LLC) cell line. C₅₇BL/6 mice with LLC model were used to study the <it>in vivo </it>antitumor effects of acetylshikonin. The expression of bax, bcl-2 and caspase-3 proteins in LLC tissue was determined with immunohistochemical staining.</p> <p>Results</p> <p>In A549, Bel-7402, MCF-7 and LLC cell lines, acetylshikonin inhibited cell growth in a dose-dependent manner. IC50 (means ± SD) were 5.6 ± 0.86 μg/ml, 6.82 ± 1.5 μg/ml, 3.04 ± 0.44 μg/ml and 2.72 ± 0.38 μg/ml respectively. Acetylshikonin suppressed tumor growth in C57BL/6 mice with LLC. The inhibition rate of acetylshikonin (2 mg/kg) was 42.85%. Immunohistochemical staining revealed that in the acetylshikonin groups the expression of bax and caspase-3 increased, whereas the expression of bcl-2 decreased, suggesting that acetylshikonin induced tumor cell apoptosis through activating the pro-apoptotic bcl-2 family and caspase-3.</p> <p>Conclusion</p> <p>Acetylshikonin isolated from <it>Arnebia euchroma (Royle) Johnst </it>cell suspension cultures exhibits specific <it>in vivo </it>and <it>in vitro </it>antitumor effects.</p

Serum albumin and albuminuria predict the progression of chronic kidney disease in patients with newly diagnosed type 2 diabetes: a retrospective study

Background Diabetes-related kidney disease is associated with end-stage renal disease and a high mortality rate. However, data on risk factors associated with kidney disease in patients with newly diagnosed type 2 diabetes mellitus (DM) remains insufficient. The aim of the present study was to identify the risk factors significantly associated with chronic kidney disease progression in patients with newly diagnosed type 2 DM. Methods We reviewed a total of 254 consecutive patients who were newly diagnosed with type 2 diabetes at Nanjing First Hospital from January to December 2014. They were observed for two years, and baseline and biochemical variables were used to identify significant predictors of kidney failure progression. Kidney failure progression was defined as a ≥ 30% increase in serum creatine level. Results The mean age of patients was 58.96 years, 37.4% were women, and 57.1% had hypertension. Kidney function progressed in 40 patients (15.75%). Multivariable logistic regression analyses showed that serum albumin (p = 0.015) and microalbuminuria (p < 0.001) were associated with kidney failure progression in patients with newly diagnosed type 2 DM. Those with lower estimated glomerular filtration rate (eGFR; 30–60 ml/min/1.73 m2) at baseline had lower serum albumin levels compared to those of patients with higher eGFR. The albuminuria levels were higher in patients with lower eGFR than in those with eGFR ≥ 90 ml/min/1.73 m2. Receiver operating characteristic curve analysis showed that the area under the curve was 0.754 (95% CI [0.670–0. 0.837]). Conclusions The overall rate of chronic kidney disease progression is relatively high, and low serum albumin and high albuminuria levels are associated with kidney failure progression in newly diagnosed diabetic patients

Roles of fasting and postprandial blood glucose in the effect of type 2 diabetes on central arterial stiffness: a 5-year prospective community-based analysis

Abstract Background Cardiovascular disease constitutes a major challenge for the health of community-dwelling population, it is essential to delay the development of atherosclerosis. However, long-term prospective studies analyzing the effect of type 2 diabetes (T2D) on central arterial stiffness are lacking, and roles of fasting and postprandial blood glucose (FBG and PBG) in this effect are controversial. Purpose of the current analysis was to investigate the effect of T2D on central arterial stiffness during the 5 years of follow-up, and explore whether both FBG and PBG were determinants of this effect in Chinese community-dwelling population. Methods The current analysis involved 898 individuals with carotid-femoral pulse wave velocity (cfPWV) ≤12 m/s. Central arterial stiffness was assessed by standard cfPWV at baseline and follow-up. Results Incidence of cfPWV >12 m/s was 21.3% (102 participants). Participants without T2D had an increase of cfPWV with a median of 0.6 m/s, whereas participants with T2D had an increase of cfPWV with a median of 1.2 m/s (p = 0.007). T2D had an independent effect on increased cfPWV in multivariate Logistic regression models (p < 0.05 for all). Elevated levels of both FBG and PBG determined the independent effect on increased cfPWV in multivariate linear regression models (p < 0.05 for all). Conclusions Type 2 diabetes had an independent effect on the development of central arterial stiffness in Chinese community-dwelling population. Both FBG and PBG should be responsible for the development of central arterial stiffness and treated as the targets of glycemic control

Combined System For Harmonic Suppression And Reactive Power Compensation

In this paper, a combined system of static var compensator (SVC) and active power filter (APF) was proposed. The system has the function of power factor correction, voltage stability, and harmonic suppression. The SVC, which consists of delta-connected thyristor-controlled reactor (TCR) and Y-connected passive power filter (PPF), is mainly for voltage stability and power factor correction. The small rating APF is used to filter harmonics generated by the nonlinear load and the TCR in the SVC and to suppress possible resonance between the grid and the PPFs. The configuration and principle of the combined system were discussed first, and then, the control method of the combined system was presented. An optimal nonlinear proportional-integral control was proposed to improve the dynamic response and decrease the steady-state error of the SVC. Harmonic detection with precompensation method and improved generalized integrator control were proposed to improve the performance of APF. The new combined system is compared to classical SVC. It is implemented in a 200-kVA prototype in the laboratory. Simulation and experimental results show that the proposed combined configuration can effectively stabilize system voltage, correct power factor, and suppress harmonic currents. © 2009 IEEE

Constructing and validating nomograms to predict risk and prognostic factors of distant metastasis in urothelial bladder cancer patients: a population-based retrospective study

Abstract Background Urothelial carcinoma is the most common type of bladder cancer worldwide and it has a poor prognosis for patients with distant metastasis. Nomograms are frequently used in clinical research, but no research has evaluated the diagnostic and prognostic factors of distant metastasis in urothelial bladder cancer (UBC). Methods The Surveillance, Epidemiology, and End Results database was used to analyze all patients diagnosed with UBC between 2000 and 2017. Lasso regression was used to identify the potential risk predictive factors for distant metastasis in UBC. Univariate and multivariate Cox proportional hazard regression analyses were performed to determine independent prognostic factors for distant metastasis urothelial bladder cancer (DMUBC). Subsequently, two nomograms were constructed based on the above models. The receiver operating characteristic (ROC), and calibration curves were performed to evaluate the two nomograms. Results The study included 73,264 patients with UBC, with 2,129 (2.9%) having distant metastasis at the time of diagnosis. In the diagnostic model, tumor size, histologic type, and stage N and T were all important risk predictive factors for distant metastasis of UBC. In the prognostic model, age, tumor size, surgery, and chemotherapy were independent factors affecting the prognosis of DMUBC. DCA, ROC, calibration, and Kaplan–Meier (K–M) survival curves reveal that the two nomograms can effectively predict the diagnosis and prognosis of DMUBC. Conclusion The developed nomograms are practical methods for predicting the occurrence risk and prognosis of distant metastasis urothelial bladder cancer patients, which may benefit the clinical decision-making process

A Dynamic Hybrid Var Compensator And A Two-Level Collaborative Optimization Compensation Method

In this paper, a dynamic hybrid var compensator (HVC) for distribution grid is proposed. The system is based on a combination of a small-capacity distribution static compensator (DSTATCOM) and multigroup large-capacity thyristor switched capacitor (TSC). The DSTATCOM is the continuous subsystem of HVC, and the TSCs are the discrete subsystem of HVC. A new hybrid control method based on expert decision has been proposed to make sure that the HVC has good performance. A two-level collaborative optimization arithmetic, which is used to decide the optimal capacity of each HVC, has been proposed in this paper. A dynamic energy-saving system based on HVCs has been developed for a melt factory in southern China; application results show that compared to traditional reactive power compensation systems, the proposed system can effectively correct power factor, support supply voltage, mitigate voltage flicker, and obtain good effect for energy saving with low cost. © 2009 IEEE

Design Considerations For Maintaining Dc-Side Voltage Of Hybrid Active Power Filter With Injection Circuit

Hybrid active power filter with injection circuit (IHAPF) shows great promise in reducing harmonics and improving power factor with a relatively low capacity active power filter, but suffers from dc-side voltage instability that inadvertently impacts the compensation performance and safety of the IHAPF. In this paper, two new methods are proposed to overcome this major technical challenge with a hysteretic control and energy release circuit, and a controllable pulsewidth modulation (PWM) rectifier. Modeling, theoretical analysis, and experimental results have verified that both methods can stabilize dc-side voltage within a certain range. A prototype IHAPF system was built incorporating the PWM rectifier dc voltage control scheme, and installed in a 220 kV substation in Southern China. It demonstrated significant improvement in harmonics reduction and power factor. The dc voltage stability issue was also resolved with the new design. © 2009 IEEE

Hemoglobin binding and antioxidant activity in spinal cord neurons: O-methylated isoflavone glycitein as a potential small molecule

Scientific community has been mesmerized by the application of bioactive O-methylated isoflavones with neuroprotective effects mediated by their antioxidant and antiapoptotic properties. The small size and planar-based structures allow them to interact with a wide range of biomolecules, such as DNA, lipids, and protein. Therefore, glycitein (C16H12O5), 4′,7-dihydroxy-6-methoxyisoflavone, as a potential antioxidant can interact with blood proteins, especially human hemoglobin (HHb), serving as a one of the main carrier proteins. To analyze this interaction, several spectroscopic techniques as well as molecular docking analysis were used. It was revealed that glycitein can interact with HHb mediated by the formation of hydrophobic forces and main aromatic residues. Also, Y140 (A), Y35 (D), and W37 (D) were displaced to a hydrophobic microenvironment upon interaction of HHb with glycitein. Furthermore, glycitein led to a slight increase in the amount of α-helix of HHb. The antioxidant assays showed that glycitein with a low concentration of 5 µM can mitigate the neurotoxicity induced by lipopolysaccharide (LPS, 100 ng/ml) in cultured spinal cord neurons, through mitigation of lactate dehydrogenase (LDH) release, downregulation of reactive oxygen species (ROS) and malonyldialdehyde (MDA) production, recovery of superoxide dismutase (SOD) and catalase (CAT) activity, and downregulation of caspase-3 protein expression and activity. In conclusion, these data indicated that glycitein with potential pharmacological activities can potentially interact with HHb, which can be of interest for future in vivo studies