Yi-Qin Shi

Synthesis, characterization and applications of calcium carbonate/fructose 1,6-bisphosphate composite nanospheres and carbonated hydroxyapatite porous nanospheres

In this work, we first investigated the effect of fructose 1,6-bisphosphate, which is fructose sugar phosphorylated on carbons 1 and 6, on the biomineralization of calcium carbonate, and prepared calcium carbonate/fructose 1,6-bisphosphate (CC/FBP) composite nanospheres. Then, we investigated the transformation of CC/FBP composite nanospheres under microwave-assisted hydrothermal conditions and prepared carbonated hydroxyapatite (CHA) porous nanospheres. We found that FBP has a unique effect on the morphology and crystallization of calcium carbonate. FBP can control the morphology of calcium carbonate and provide the phosphorus source for the formation of CHA. The morphology and size of CC/FBP composite nanospheres can be preserved after transformation to CHA porous nanospheres under microwave-assisted hydrothermal conditions. The CC/FBP composite nanospheres and CHA porous nanospheres are efficient for anticancer drug (docetaxel) loading and release, and the drug delivery system shows a high ability to damage tumor cells, and thus is promising for application in drug delivery. The as-prepared CC/FBP composite nanospheres and CHA porous nanospheres have excellent biocompatibility and high protein adsorption capacity, as well as high efficiency for gene transfection.

Arterial Baroreflex Dysfunction Impairs Ischemia-Induced Angiogenesis

Background Endothelium‐derived acetylcholine (eACh) plays an important role in the regulation of vascular actions in response to hypoxia, whereas arterial baroreflex (ABR) dysfunction impairs the eACh system. We investigated the effects of ABR dysfunction on ischemia‐induced angiogenesis in animal models of hindlimb ischemia with a special focus on eACh/nicotinic ACh receptor (nAChR) signaling activation. Methods and Results Male Sprague‐Dawley rats were randomly assigned to 1 of 3 groups that received (1) sham operation (control group), (2) sinoaortic denervation (SAD)‐induced ABR dysfunction (SAD group), or (3) SAD rats on diet with an acetylcholinesterase inhibitor pyridostigmine (30 mg/kg per day, SAD+Pyr group). After 4 weeks of the SAD intervention, unilateral limb ischemia was surgically induced in all animals. At postoperative day 14, SAD rats exhibited impaired angiogenic action (skin temperature and capillary density) and decreased angiogenic factor expressions (vascular endothelial growth factor [VEGF] and hypoxic inducible factor [HIF]‐1α) in ischemic muscles. These changes were restored by acetylcholinesterase inhibition. Rats with ABR dysfunction had lower eACh levels than did control rats, and this effect was recovered in SAD+Pyr rats. In α7‐nAChR knockout mice, pyridostigmine improved ischemia‐induced angiogenic responses and increased the levels of VEGF and HIF‐1α. Moreover, nicotinic receptor blocker inhibited VEGF expression and VEGF receptor 2 phosphorylation (p‐VEGFR2) induced by ACh analog. Conclusions Thus, ABR dysfunction appears to impair ischemia‐induced angiogenesis through the reduction of eACh/α7‐nAChR‐dependent and ‐independent HIF‐1α/VEGF‐VEGFR2 signaling activation.

A new method for assessing variability of 24 h blood pressure and its first application in 1526 elderly men

1 Blood pressure variability (BPV) includes physiological and random variations in blood pressure (BP). Commonly used approaches, such as standard deviation (SD) and weighted standard deviation (wSD) methods, do not efficiently assess random variation in BP. In the present study, we propose a novel method to assess individual BP variations, extracting random variation in BP by eliminating physiological variation mathematically. This novel assessment method furthers our understanding of the relationship between BP variation and lacunar infarction (LACI). 2 In the present study, we analysed ambulatory blood pressure monitoring recordings taken from 1526 men aged 60–98 years of age. Individual curves were created using a mathematical method and the related BP variation calculated, namely the SD for individual BP variations. In addition, correlations between LACI and BP variations as determined by the classical SD method, wSD and our novel assessment method (SD′) were evaluated. 3 The results demonstrated that 24 h variations in systolic BP (SBP) were closely associated with LACI when the SD and wSD methods were used (P < 0.05), but the most significant correlations were observed when the SD′ method was used (P < 0.01). Furthermore, using SD′ yielded the lowest value of the parameter P among the three different methods used to analyse BPV. Using the SD′ method, a significant correlation was found between variations in SBP and the incidence of LACI (P < 0.05). It was found that the incidence of LACI increaesd by 2% with each 1 mmHg increase in SBP variation. 4 In conclusion, our novel assessment method enables mathematical removal of interference from physiological BP variation and the results show a better correlation with LACI. Thus, our novel method may be considered a simple index of 24 h BP variation that is superior to conventional SD and wSD methods.

Noninvasive blood glucose sensing on human body with near-infrared reflection spectroscopy

The non-invasive blood glucose sensing method has shown its high impact on the clinic application. This can make the measurement on the clinically relevant concentrations of glucose be free from the pain of patient. The transmission spectrum study indicates that the dependence of glucose concentration on the absorbance is in linear manner for the glucose concentration in the region of 30mg/dL to 4.5×104mg/dL. By the near infrared reflection spectroscopy of fiber spectrometer, the reflection band between 1.2μm and 1.35μm can be used to correlated with the glucose concentration in the range of 30 to 300 mg/dL. This reflection band is finally used to measure the glucose concentration effect in non-invasive manner, which gives the statistical significance of P value 0.02. Our experiment result shows that it is possible to get the glucose concentration by the near infrared reflection spectrum measurement on the human forefinger. This non-invasive blood glucose sensing method may useful in clinic after more experiment for different people.

Beyond autonomic neuromodulation: Acetylcholinesterase inhibitor against peripheral artery disease

The acetylcholinesterase inhibitor (AChEI)-based therapeutic strategies have been shown to have vasculoprotective properties in the animal model of hindlimb ischemia due to its activation of the endothelial cholinergic system. However, little is know about whether other cell types (myocytes, immunocytes) are involved in the AChEI-related therapeutic benefits in peripheral artery disease. Therefore, we review the multiple cell-targeted effects of AChEI on the animal model of hindlimb ischemia and explore its clinical application in angiomyogenesis.

A New Index to Predict the Incidence of Cerebral Infarction

Correspondence Dr. Jun-Li Duan, Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China. Tel.: +86-21-2507 8999; Fax: +86-21-6551 7520; E-mail: duanjunlixh@163.com or junlishanghai2005@yahoo.com.cn and Dr. Wei Lu, National Lab for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, 500 Yu-Tian Road, Shanghai 200083, China. Tel.: +86-21-5538 3993; Fax: +86-21-6583 0734; E-mail: luwei@mail.sitp.ac.cn

Nonnegative matrix factorization numerical method for integrated photonic cavity based spectroscopy

Nonnegative matrix factorization numerical method has been used to improve the spectral resolution of integrated photonic cavity based spectroscopy. Based on the experimental results for integrated photonic cavity device on Optics Letters 32, 632 (2007), the theoretical results show that the spectral resolution can be improved more than 3 times from 5.5 nmto 1.8 nm. It is a promising way to release the difficulty of fabricating high-resolution devices.

ASSA14-05-01 Therapeutic Ultrasound Augments Postnatal Neovascularization in Mice Model of Hindlimb Ischemia

Background Therapeutic ultrasound (TUS) has been proposed as a potential strategy to accelerate proliferation and regeneration to the damaged tissue. However, the underline mechanism remains modest clarified. The purpose of this study was to determine the mechanism of TUS on ischemia-induced angiogenesis using mice model of hindlimb ischemia. Methods and results Hindlimb ischemia was induced by unilateral femoral artery resection using 8–12 week-old male C57BL6 mice. External TUS (1.0 MHz, 0.3W/cm2) was then performed for 9 min/day. At postoperative day 14, decreased prevalence of gangrene, increased capillary density and skin temperature ratio between ischaemic/normal extremities were observed in TUS-treated mice. Moreover, the levels of nitric oxide (NO) expression, endothelial nitric oxide synthase (eNOS) and Akt phosphorylation contained in the ischaemic muscles were increased in response to TUS. In vitro, TUS interrupted the process of hypoxia-induced apoptosis and contributed to the tube-formative and proliferative capacities of human umbilical vein endothelial cells. TUS increased the level of NO in the conditioned media, as well as the eNOS and Akt phosphorylation in the cell lysate. Finally, administration of PI3K inhibitor LY294002 and NG-Nitro-L-arginine Methyl Ester (L-NAME) could block these TUS-mediated angiogenic benefits. Conclusions In conclusion, the present study indicates that external ultrasound exposure contributes to ischemia-induced neovascularization through promoting endothelial functions via Akt-eNOS signal pathway.

ASSA14-15-01 Angiogenesis effect of therapeutic ultrasound on ischaemic hind limb in mice

Background Therapeutic ultrasound (TUS) has been proposed as a potential strategy for therapeutic revascularisation. However, the specific mechanism remains to be explored in detail. The purpose of this study was to determine the mechanism of TUS on ischaemic angiogenesis in mice with acute ischaemic hind limb and proliferation, migration, tube formation and potential signalling pathways of human umbilical vein endothelial cells (HUVECs). Methods TUS was set by a combination of various ultrasound-related variables: frequency of 1.0 MHz; intensity of 0.3 W/cm2; exposure time of 3, 6, or 9 min. We stimulated the HUVECs in culture daily with TUS for 3 days. The effects of therapeutic ultrasound on HUVECs proliferation were evaluated using the CCK-8 assay. Cell migration was assayed by scratch test. Angiogenesis was observed by tube formation assay. The potential involvement of PI3K-Akt-eNOS signalling pathways was explored using selective chemical inhibitor or Western-blot analysis. Left femoral artery ligation was used to establish the model of acute hind limb ischaemic in mice (C57BL/6J male mice, 18–22 g, 2–3 months old), TUS was exposed subcutaneously once everyday for 14 days. The mice were randomly divided into four experimental groups: sham operated group; TUS 3 min group; TUS 6 min group and TUS 9 min group. The experiment was carried out on the 1st and14th after ligation. To determine whether TUS affected the angiogenesis activity of mice with ischaemic hind limb, we measured temperature of hind limb by using infrared thermometer, and microvessel density (MVD) was determined by CD31 staining. Results The results show that proliferation, migration and tube formation in HUVECs could be promoted by TUS at exposure time of 9 min, and inhibited by NG-Nitro-L-arginine Methyl Ester (L-NAME). eNOS and p-eNOS expression increased significantly when TUS 9 min was added, but could be attenuated by L-NAME. p-Akt expression augmented by TUS at exposure time of 9 min, but could be inhibited by LY294002. Compared to the temperature of hind limb, the group of TUS 9 min at the 14th was increased, while TUS 6 min group increased, but only TUS 9 min was there a significant difference. Except that, the MVD was promoted in TUS 9 min group significantly. Conclusions In conclusion, the present study indicates that 9 min of exposure to TUS promote angiogenesis among ischaemic hind limb in mice and that this process is mediated through the PI3K-Akt-eNOS signal pathway in ECs.

ASSA14-03-01 Pulsed Electromagnetic Field Improves Postnatal Neovascularization in Response to Hindlimb Ischemia

Background Pulsed electromagnetic fields (PEMF) have been shown to accelerate proliferation and regeneration to the damaged tissue, but its mechanism remains unclear. Here, we examine whether PEMF therapy improves postnatal neovascularization using murine model of hindlimb ischemia, and investigate the underlying cellular/molecular mechanisms. Methods and Results Hindlimb ischemia was induced by unilateral femoral artery resection using 6–8 week-old male C57BL6 mice. PEMF therapy (8 min/cycle, 30 ± 3 Hz, 5 mT) was then performed 4 cycles/day. At postoperative day 21, accelerated wound healing, decreased prevalence of gangrene and increased capillary density were observed among the PEMF-exposed mice. Moreover, the levels of vascular endothelial growth factor (VEGF) expression, endothelial nitric oxide synthase (eNOS) and Akt phosphorylation contained in the ischaemic muscles were increased in response to PEMF therapy. In vitro , PEMF interrupted the process of hypoxia-induced apoptosis and contributed to the tube-formative and proliferative capacities of human umbilical vein endothelial cells. PEMF exposure increased the level of VEGF in the conditioned media, as well as the eNOS and Akt phosphorylation in the cell lysate, and these PEMF-mediated angiogenic benefits could be blocked after PI3K inhibitor was administrated. Conclusions In conclusion, Our data indicated that PEMF enhanced ischemia-mediated angiogenesis, through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway. Therefore, PEMF may be valuable for the treatment of the patients with critical limb ischemia.