Oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line

Oridonin, a diterpenoid isolated from Rabdosia rubescencs, has been reported to have antitumor effects. However, low solubility has limited its clinical applications. Preparation of drugs in the form of nanosuspensions is an extensively utilized protocol. In this study, we investigated the anticancer activity of oridonin and oridonin nanosuspension on human pancreatic carcinoma PANC-1 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to investigate the effect of oridonin on cell growth. Propidium iodide and Hoechst 33342 staining were used to detect morphologic changes. The percentage of apoptosis and cell cycle progression was determined by flow cytometric method staining with propidium iodide. Annexin V-fluorescein isothiocyanate (FITC)/PI staining was used to evaluate cell apoptosis by flow cytometry. Caspase-3 activity was measured by spectrophotometry. The apoptotic and cell cycle protein expression were determined by Western blot analysis. Both oridonin and oridonin nanosuspension induced apoptosis and G2/M phase cell cycle arrest, and the latter had a more significant cytotoxic effect. The ratio of Bcl-2/Bax protein expression was decreased and caspase- 3 activity was stimulated. The expression of cyclin B1 and p-cdc2 (T161) was suppressed. Our results showed that oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line

A coupled hydro-thermo-mechanical model based on TLF-SPH for simulating crack propagation in fractured rock mass

Abstract In this paper, a hydro-thermo-mechanical coupling model based on the smoothed particle hydrodynamics with total Lagrangian formula (HTM-TLF-SPH) is proposed to simulate the crack propagation and instability process of fractured rock mass. TLF-SPH uses the Lagrangian kernel approximation, that is, the kernel function and its gradient need only be calculated once in the initial configuration, which is much more efficient than the smoothed particle hydrodynamics (SPH) based on the Euler kernel approximation. In TLF-SPH, particles interact with each other through virtual link, and the crack propagation path of rock mass is tracked dynamically by capturing the fracture of virtual link. Firstly, the accuracy and robustness of the HTM-TLF-SPH coupling model are verified by a reference example of drilling cold shock, and the simulation results agree well with the analytical solutions. Then, the crack propagation law of surrounding rock and the evolution characteristics of physical fields (displacement, seepage and temperature fields) after excavation and unloading of deep roadway under the coupling condition of hydro-thermo-mechanical are investigated. In addition, the seepage and heat transfer processes of the surrounding rock of Daqiang coal mine under different coupling conditions are successfully simulated. Meanwhile, the effect of the boundary water pressure difference on the temperature and seepage fields under the hydro-thermal coupling condition is quantitatively analyzed

Fuzzy Optimized MFAC Based on ADRC in AUV Heading Control

The control issue of Autonomous Underwater Vehicles (AUV) is very challenging since the precise mathematical model of AUV is hard to establish due to its strong coupling and time-varying features. Meanwhile, AUV movement is easily interfered with by ocean currents and waves, causing anti-interference performance of traditional Proportional-Integral-Derivative (PID) control to be unsatisfactory. Aiming to solve those problems, an algorithm of fuzzy optimized model-free adaptive control (MFAC) based on auto-disturbance rejection control (ADRC) was proposed and used in AUV heading control. The MFAC is used to overcome the difficulty with establishing a precise mathematical model, and the ADRC is introduced to handle the interference of currents and waves. In this paper, MFAC and ADRC are combined. First, the MFAC is performed based only on the I/O data of the controlled object, which is simple to implement with low calculation complexity and strong robustness. Then, a tracking differentiator (TD) is employed to track the input signal to overcome the antinomy of rapidity and hypertonicity in MFAC. After that, an extended-state observer (ESO) is added to control the variables of MFAC to estimate all the disturbances, which can greatly improve the anti-interference ability of the system. Due to the complexity and diversity of the marine environment, a fuzzy optimized MFAC based on ADRC is proposed to improve the adaptability of AUV to the marine environment. Simulations and experiments were carried out to verify the control effect of this algorithm in complex sea conditions

Development and in vitro evaluation of deacety mycoepoxydiene nanosuspension

National Basic Research Program of China (973 Program) [2009CB930300]; Major scientific and technological specialized project for Significant New Formulation of New Drugs [2009ZX09502-001]Deacety mycoepoxydiene (DM), extracted from Phomopsis sp. A123 of thalassiomycetes, is a novel and potent anti-cancer agent. Due to its physicochemical characteristics, the drug, a poorly water-soluble weak acid, shows poor solubility and dissolution characteristics. To improve the solubility and dissolution, formulation of DM as nanosuspension has been performed in this study. Nanosuspensions were developed by high-pressure homogenization (HPH) (DissoCubes (R) Technology) and transformed into dry powder by freeze-drying. The nanosuspension produced was then investigated using optical microscope, photon correlation spectroscopy (PCS), zeta potential measurement, SEM, TEM, AFM, DSC and XRD. To verify the theoretical hypothesis on the benefit of increased surface area, in vitro saturation solubility and dissolution profile were investigated. In addition, the in vitro cell cytotoxicity was examined. Results showed that a narrow size distributed nanosuspension composed of unchanged crystalline state with a mean particle size of 515 +/- 18 nm, a polydispersity index of 0.12 +/- 0.03 and a zeta potential of -23.1 +/- 3.5 mV was obtained. In the in vitro dissolution test an accelerated dissolution velocity and increased saturation solubility could be shown for the MD nanosuspension. The in vitro cytotoxicity experiments provided evidence for an enhanced efficacy of the DM nanosuspension formulation compared to free DM solution. Taken together, these results illustrate the opportunity to formulate DM in nanosuspension form as an anti-prostate cancer delivery system. (C) 2010 Published by Elsevier B.V

Studies on the preparation, characterization and pharmacokinetics of Amoitone B nanocrystals

Amoitone B, as a new derivative of cytosporone B, has been proved to be a natural agonist for Nur77. It exhibits remarkable anticancer activity in vivo and has the potential to be a therapeutic agent for cancer treatment. However, the poor solubility and dissolution rate result in low therapeutic index for injection and low bioavailability for oral administration, therefore limiting its application. In order to magnify the clinical use of Amoitone B, nanocrystal was selected as an application technology to solve the above problems. In this study, the optimized Amoitone B nanocrystals with small and uniform particle size were successfully prepared by microfluidization method and investigated by morphology, size distribution, and zeta potential. The differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed there was no crystalline state changed in the size reduction process. For Amoitone B nanocrystals, an accelerated dissolution velocity and increased saturation solubility were achieved in vitro and a markedly different pharmacokinetic property in vivo was exhibited with retarded clearance and magnified AUC compared with Amoitone B solution. These results implied that developing Amoitone B as nanocrystals is a promising choice for intravenous delivery and further application for cancer therapy. (C) 2012 Elsevier B. V. All rights reserved.National Basic Research Program of China (973Program) [2009CB930300

Long-term care status for the elderly with different levels of physical ability: a cross-sectional survey in first-tier cities of China

Abstract Background Long term care (LTC) services for functionally impaired senior citizens are crucial for addressing the challenges of aging. However, research on eligibility criteria and coverage of LTC in China is lacking. Our objective is to assess the current status of LTC and explore eligibility criteria and coverage for the elderly. Methods This is a cross-sectional study conducted in two first-tier cities in China. Residents aged 65 or over were recruited from a nursing home and four primary hospitals. Participants were divided into three groups (bedridden, domestic, and community), then six grades (grade one to six) according to the Longshi Scale, and their functional ability was assessed using the Modified Barthel Index. Information such as diseases, complications, and daily care needs were collected. Nursing staff were invited to indicate patients’ needs for care. A one-way ANOVA test, Kruskal Wallis H test and Mann–Whitney U test were used to explore the differences of variables in three Longshi groups or Longshi grades. Results Among all 1157 participants, with an average age of 80.54, 69.3% were in the bedridden group. The most common diagnosis was stroke (71.4%), with the most prevalent complication being pulmonary infection (25.2%). In the nursing assessment, basic health care, disease care, activity care, complication prevention care and psychosocial care were summarized as the five main aspects of LTC for the elderly. Feeding, bathing, drinking, bowel management and bladder management were identified as the basic care which fulfills participants’ basic physical needs in each Longshi group. Mouth care, artificial airway management, and body reposition, which can prevent immobility complications, were highly demanded by bedridden elderly. Conclusions The elderly in grade one to three are the ones in need of LTC most. The content of LTC for elderly should include basic care which fulfills their basic physical needs and complication care which can prevent immobility complications. The evidence of this research may contribute to the design of LTC in China. Trial registration The study design was registered in the Chinese Clinical Trial Registry (ChiCTR-2000034067, Registered 22 Jun 2020, http://www.chictr.org.cn/showproj.aspx?proj=54770 )