Jun-Li Duan

MicroRNA‐124 Protects Neurons Against Apoptosis in Cerebral Ischemic Stroke

To explore the role and underlying mechanism of miR‐124 in stroke.

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.

Curcumin as therapeutics for the treatment of head and neck squamous cell carcinoma by activating SIRT1.

SIRT1 is one of seven mammalian homologs of Sir2 that catalyzes NAD+-dependent protein deacetylation. The aim of the present study is to explore the effect of SIRT1 small molecule activator on the anticancer activity and the underlying mechanism. We examined the anticancer activity of a novel oral agent, curcumin, which is the principal active ingredient of the traditional Chinese herb Curcuma Longa. Treatment of FaDu and Cal27 cells with curcumin inhibited growth and induced apoptosis. Mechanistic studies showed that anticancer activity of curcumin is associated with decrease in migration of HNSCC and associated angiogenesis through activating of intrinsic apoptotic pathway (caspase-9) and extrinsic apoptotic pathway (caspase-8). Our data demonstrating that anticancer activity of curcumin is linked to the activation of the ATM/CHK2 pathway and the inhibition of nuclear factor-κB. Finally, increasing SIRT1 through small molecule activator curcumin has shown beneficial effects in xenograft mouse model, indicating that SIRT1 may represent an attractive therapeutic target. Our studies provide the preclinical rationale for novel therapeutics targeting SIRT1 in HNSCC.

Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinoma in vitro and in vivo through ATM/Chk2/p53-dependent pathway

Studies have demonstrated that curcumin (CUR) exerts its tumor suppressor function in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). However, the exact underlying molecular mechanisms remain obscure. Here, we aim to test whether CUR affects ATM/Chk2/p53 signaling pathway, leading to the induction of cell cycle arrest, inhibition of angiogenesis of HNSCC in vitro and in vivo. To this end, we conducted multiple methods such as MTT assay, Invasion assay, Flow cytometry, Western blotting, RT-PCR, and transfection to explore the functions and molecular insights of CUR in HNSCC. We observed that CUR significantly induced apoptosis and cell cycle arrest, inhibited angiogenesis in HNSCC. Mechanistically, we demonstrated that CUR markedly up-regulated ATM expression and subsequently down-regulated HIF-1α expression. Blockage of ATM production totally reversed CUR induced cell cycle arrest as well as anti-angiogenesis in HNSCC. Moreover, our results demonstrated that CUR exerts its antitumor activity through targeting ATM/Chk2/p53 signal pathway. In addition, the results of xenograft experiments in mice were highly consistent with in vitro studies. Collectively, our findings suggest that targeting ATM/Chk2/p53 signal pathway by CUR could be a promising therapeutic approach for HNSCC prevention and therapy.Studies have demonstrated that curcumin (CUR) exerts its tumor suppressor function in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). However, the exact underlying molecular mechanisms remain obscure. Here, we aim to test whether CUR affects ATM/Chk2/p53 signaling pathway, leading to the induction of cell cycle arrest, inhibition of angiogenesis of HNSCC in vitro and in vivo. To this end, we conducted multiple methods such as MTT assay, Invasion assay, Flow cytometry, Western blotting, RT-PCR, and transfection to explore the functions and molecular insights of CUR in HNSCC. We observed that CUR significantly induced apoptosis and cell cycle arrest, inhibited angiogenesis in HNSCC. Mechanistically, we demonstrated that CUR markedly up-regulated ATM expression and subsequently down-regulated HIF-1α expression. Blockage of ATM production totally reversed CUR induced cell cycle arrest as well as anti-angiogenesis in HNSCC. Moreover, our results demonstrated that CUR exerts its antitumor activity through targeting ATM/Chk2/p53 signal pathway. In addition, the results of xenograft experiments in mice were highly consistent with in vitro studies. Collectively, our findings suggest that targeting ATM/Chk2/p53 signal pathway by CUR could be a promising therapeutic approach for HNSCC prevention and therapy.

Magnesium whitlockite hollow microspheres: a comparison of microwave-hydrothermal and conventional hydrothermal syntheses using fructose 1,6-bisphosphate, and application in protein adsorption

Magnesium whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) is an abundant and biologically important biomineral in living bone, but the synthesis of single-phase WH hollow microspheres (WHHMs) still remains a challenge. In this paper, we report the environmentally friendly rapid microwave-assisted hydrothermal synthesis of WHHMs using fructose 1,6-bisphosphate trisodium salt as a biocompatible organic phosphorus source. In addition, the conventional hydrothermal method is also adopted for the synthesis of WHHMs, and the two synthetic methods are compared and discussed. The effects of the synthesis methods and experimental conditions on the crystal phase, morphology, stability and cytotoxicity of the products are investigated. The results indicate that the as-prepared WHHMs have a high biocompatibility. Moreover, the as-synthesized WHHMs are explored for potential application in protein adsorption by using hemoglobin (Hb) as a model protein, and they exhibit a relatively high protein adsorption capacity, thus, they are promising for applications in various biomedical fields such as protein adsorption.

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.

Donepezil Protects Endothelial Cells against Hydrogen Peroxide-Induced Cell Injury

Vascular endothelial cells serve as a barrier between tissue and blood stream, which plays an important role in maintaining vascular homeostasis. Oxidative stress has been implicated as a major cause of endothelial injuries in a variety of clinical abnormalities including artherosclerosis, ischemia reperfusion injury, and diabetes [1]. Donepezil, a reversible noncompetitive acetylcholinesterase inhibitor, used to treat Alzheimer’s disease, has been reported that it could protect neuronal cells against cell injury [2]. In this study, the protective effect of donepezil against hydrogen peroxide (H2O2)-induced cell injury in vitro was determined. Human umbilical vein endothelial cell (HUVEC) line obtained from Department of Pharmacology, College of Pharmacy, Second Military Medical University, was cultured in RPMI-1640 medium (Gibco, NY, USA), containing 10% fetal bovine serum (Gibco, NY, USA), 100 U/mL penicillin (Invitrogen, NY, USA), and 100 μg/mL streptomycin (Invitrogen, NY, USA). Cells were grown in a 37◦C, 5% CO2 incubator with media replenishment every 3 days. Before experimental intervention, confluent cultured cells were preincubated for 12 h in starved medium. The starved cells were then divided into four experimental groups: (1) control; (2) cells incubated with H2O2 (100 μM) (Sinopharm Chemical Reagent Co. Ltd, China) 1.5 h alone; (3) cells pretreated with donepezil (Sigma, MO, USA) for 1 h before coincubated with H2O2; (4) cells incubated with donepezil alone. To evaluate HUVEC cell viability, MTT assay was conducted. After being treated with different medium conditions, the hypoxia-inducible factor alpha (HIF1α) and manganese superoxide dismutase (MnSOD) expression in HUVECs were analyzed by Western blot. Levels of basic fibroblast growth factor (bFGF) and stromal-derived factor-1 (SDF-1) in cellular supernatant of each group were determined by ELISA kits (R&D Systems, MN, USA). All data are presented as mean ± SD. Comparisons of the groups were evaluated by using the t-test with one-way analysis of variance (ANOVA). Statistical significance was set at P < 0.05.

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.

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