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Zhang Z.,University of Connecticut | Zhang Z.,National Institutes for Food and Drug Control | Chen N.,University of Connecticut | Li S.,University of Connecticut | And 2 more authors.
Journal of the American Chemical Society | Year: 2012

The ability to regulate cell-material interactions is important in various applications such as regenerative medicine and cell separation. This study successfully demonstrates that the binding states of cells on a hydrogel surface can be programmed by using hybridized aptamers and triggering complementary sequences (CSs). In the absence of the triggering CSs, the aptamers exhibit a stable, hybridized state in the hydrogel for cell-type-specific catch. In the presence of the triggering CSs, the aptamers are transformed into a new hybridized state that leads to the rapid dissociation of the aptamers from the hydrogel. As a result, the cells are released from the hydrogel. The entire procedure of cell catch and release during the transformation of the aptamers is biocompatible and does not involve any factor destructive to either the cells or the hydrogel. Thus, the programmable hydrogel is regenerable and can be applied to a new round of cell catch and release when needed. © 2012 American Chemical Society.


Li S.,University of Connecticut | Chen N.,University of Connecticut | Zhang Z.,University of Connecticut | Zhang Z.,National Institutes for Food and Drug Control | Wang Y.,University of Connecticut
Biomaterials | Year: 2013

Rare circulating tumor cells are a promising biomarker for the detection, diagnosis, and monitoring of cancer. However, it remains a challenge to develop biomedical devices for specific catch and nondestructive release of circulating tumor cells. The purpose of this study was to explore a unique system for cell catch and release by using aptamer-functionalized hydrogels and restriction endonucleases. The results show that the hydrogel coating was highly resistant to nonspecific cell binding with ∼5-15 cells/mm2 on the hydrogel surface. In contrast, under the same condition, the aptamer-functionalized hydrogel coating could catch target cancer cells with a density over 1000 cells/mm2. When the hydrogel coating was further treated with the restriction endonucleases, the bound cells were released from the hydrogel coating because of the endonuclease-mediated sequence-specific hydrolysis of the aptamer sequences. The release efficiency reached ∼99%. Importantly, ∼98% of the released cells maintained viability. Taken together, this study demonstrates that it is promising to apply endonuclease-responsive aptamer-functionalized hydrogels as a coating material to develop medical devices for specific catch and nondestructive release of rare circulating tumor cells. © 2012 Elsevier Ltd.


Ma S.,Shanghai JiaoTong University | Xie N.,Shanghai JiaoTong University | Li W.,Shanghai JiaoTong University | Yuan B.,National Institutes for Food and Drug Control | And 3 more authors.
Cell Death and Differentiation | Year: 2014

Mesenchymal stem cells (MSCs) can be isolated from almost all tissues and effectively expanded in vitro. Although their true in situ properties and biological functions remain to be elucidated, these in vitro expanded cells have been shown to possess potential to differentiate into specific cell lineages. It is speculated that MSCs in situ have important roles in tissue cellular homeostasis by replacing dead or dysfunctional cells. Recent studies have demonstrated that in vitro expanded MSCs of various origins have great capacity to modulate immune responses and change the progression of different inflammatory diseases. As tissue injuries are often accompanied by inflammation, inflammatory factors may provide cues to mobilize MSCs to tissue sites with damage. Before carrying out tissue repair functions, MSCs first prepare the microenvironment by modulating inflammatory processes and releasing various growth factors in response to the inflammation status. In this review, we focus on the crosstalk between MSCs and immune responses and their potential clinical applications, especially in inflammatory diseases. © 2014 Macmillan Publishers Limited.


Geng Y.,Hebei University | Zhao C.,National Institutes for Food and Drug Control | Huang W.,National Institutes for Food and Drug Control | Harrison T.J.,University College London | And 3 more authors.
Journal of Hepatology | Year: 2016

Background & Aims Hepatitis E virus (HEV) is known to be excreted in the stool but there has been no report of its presence in urine. This study investigated the presence of HEV RNA and antigen (HEV-Ag) in urine and its possible transmission. Methods Serum and urine samples from patients with chronic or acute HEV infection and HEV infected monkeys were tested for viral and biochemical markers. Liver and kidney biopsies from the infected monkeys were analyzed by histopathology and immunohistochemistry. The infectivity of HEV from urine was assessed by inoculation into monkeys. Results HEV RNA and HEV-Ag were detected persistently in the urine of a patient with chronic HEV infection. Subsequently, HEV RNA was detected in the urine of three of the eight (37.5%) acute patients, all of whom had detectable HEV-Ag in their urine. HEV RNA and HEV-Ag were also detectable in the urine of HEV infected monkeys. The ratio of HEV-Ag to RNA in the urine of the infected monkeys was significantly higher than in their sera and feces. The parameters of routine urinalysis remained within the normal ranges in the hepatitis E patients and infected monkeys, however, pathological changes and HEV-Ag were observed in the kidneys of the infected monkeys. Furthermore, one of two monkeys became infected with HEV after inoculation with urine from another infected monkey. Conclusions HEV infection may result in kidney injury and the urine may pose a risk of transmission. HEV-Ag detection in urine may be valuable for diagnosis of ongoing HEV infection. © 2015 European Association for the Study of the Liver.


Wang Y.-P.,National Institutes for Food and Drug Control
Chinese Journal of Biologicals | Year: 2012

Objective: To evaluate the effect of aluminum hydroxide adjuvant on cellular immune response induced with inactivated enterovirus 71 (EV71) in mice. Methods: BALB/c mice were immunized with aluminum hydroxide adjuvant-containing and adjuvant-free inactivated EV71 vaccines respectively, using physiological saline as control. Blood samples were collected 7 d after booster immunization, from which mononuclear cells (MNCs) were isolated and CD8+ T cells were removed. The secretion level of IFNγ by mouse splenic MNCs after stimulation with bulk EV71 vaccine or VPI-36 was determined by ELISPOT, while those of IL-2, IL-4, IL-5, IL-6 and IL-10 by LUMINEX technique. The serum neutralizing antibody titers of mice were determined by micro-neutralization test in vitro. Results: The number of spot-forming cells (SFCs) of IFNγ secreted by MNCs of BALB/c mice immunized twice with aluminum hydroxide adjuvant -containing EV71 vaccine were significantly higher than those with adjuvant-free vaccine (P < 0.05). Both the positive conversion rates of neutralizing antibody against EV71 in sera of mice immunized with aluminum hydroxide adjuvant-containing and adjuvant-free vaccines were 100%. However, the neutralizing antibody titer induced by aluminum hydroxide adjuvant-containing was significantly higher than that by adjuvant-free vaccine (P < 0.01). Conclusion: Inactivated EV71 vaccine induced secretion of specific IFNγ, IL-2, IL-6 and IL-10, and aluminum hydroxide adjuvant enhanced Th1 and Th2 immune responses induced by inactivated EV71 vaccine.


He P.,National Institutes for Food and Drug Control | Zou Y.,Sinovac Research & Development Co Ltd | Hu Z.,National Institutes for Food and Drug Control
Human Vaccines and Immunotherapeutics | Year: 2015

In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully understood. Current explanations for the mode of action of aluminum hydroxide-based adjuvants include, among others, the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway. These collectively galvanize innate as well as acquired immune responses and activate the complement system. Factors that have a profound influence on responses evoked by aluminum hydroxide-based adjuvant applications include adsorption rate, strength of the adsorption, size and uniformity of aluminum hydroxide particles, dosage of adjuvant, and the nature of antigens. Although vaccines containing aluminum hydroxide-based adjuvants are beneficial, sometimes they cause adverse reactions. Further, these vaccines cannot be stored frozen. Until recently, aluminum hydroxide-based adjuvants were known to preferentially prime Th2-type immune responses. However, results of more recent studies show that depending on the vaccination route, aluminum hydroxide-based adjuvants can enhance both Th1 as well as Th2 cellular responses. Advances in systems biology have opened up new avenues for studying mechanisms of aluminum hydroxide-based adjuvants. These will assist in scaling new frontiers in aluminum hydroxide-based adjuvant research that include improvement of formulations, use of nanoparticles of aluminum hydroxide and development of composite adjuvants.


Zhang S.-Q.,National Institutes for Food and Drug Control | Fan Y.-M.,National Institutes for Food and Drug Control
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2012

A sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the determination of andrographolide sodium bisulphite (ASB) in dog plasma using dehydroandrographolide (DAG) as an internal standard. Chromatographic separation was achieved on a Hypersil Gold C18 column (50mm×2.1mm, 1.9μm) with gradient elution that consisted of methanol and water at a flow rate of 0.2mL/min. Quantification was done using selected reaction monitoring (SRM) mode to monitor precursor-product ion transitions of m/z 413.2→287.2 for ASB and 331.2→303.3 for DAG at negative ionization mode. Good linearity was obtained over the range of 10-1000ng/mL and the correlation coefficient was better than 0.99. The intra- and inter-day accuracies ranged from 97.2% to 107.8% and precisions (RSD) were within 13.9%. ASB was found stable under three freeze-thaw cycles, short-term temperature, post-preparative and long-term temperature conditions. The method was successfully applied to a pharmacokinetic study of ASB intravenously administered to Beagle dogs. © 2012 Elsevier B.V.


He P.,National Institutes for Food and Drug Control
Chinese Journal of Biologicals | Year: 2011

Objective: To investigate the antigen-specific cytokine responses induced by various kinds of hepatitis B (HB) vaccines in mice as well as the TH1 cytokine-secreting ability of mononuclear cells, and evaluate the immunogenicities of the vaccines. Methods: BALB/c mice (H-2 d) were immunized with recombinant Hansenula polymorpha (HP)-, Saccharomyces cerevisiae (SC)- and CHO cells-derived HB vaccines respectively. The splenic mononuclear cells (MNCs) of mice were isolated 4, 7, 10, 14, 25 and 35 d after immunization respectively, stimulated with HBsAg in vitro, and determined for IFN-γ, IL-2 and TNF-α levels by Luminex method. Results: The IFN-γ and TNF-α levels of mice induced by the three kinds of HB vaccine reached peak values 10 d after immunization then decreased, while the IL-2 level increased gradually. The IFNγ levels 10 and 14 d after immunization with SC-derived vaccine (P < 0.01), the IL-2 levels 10, 25 and 35 d after immunization with HP-derived vaccine (P < 0.05), the TNF-α levels 10, 14 and 35 d after immunization with SC-derived vaccine(P < 0.05) as well as the TNF-α levels 7 and 25 d after immunization with HP-derived vaccine (P < 0.05) were significantly higher than those with CHO cells-derived vaccine. Conclusion: The levels and changing tendencies of cellular immune responses in mice induced by various kinds of HB vaccine were different. The TH1 cytokine level induced by yeast-derived vaccine was higher than that by CHO cells-derived vaccine.


Zhang S.-Q.,National Institutes for Food and Drug Control
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2011

A sensitive and selective liquid chromatographic-tandem mass spectrometric method was developed for quantification of triamcinolone acetonide (TA) in rabbit ocular tissues. After a simple liquid-liquid extraction using tert-butyl methyl ether, TA and internal standard methylprednisolone were separated on a C 18 column with a mobile phase of acetonitrile:water:formic acid (60:40:0.1, v/v/v) and quantified by the use of selected reaction monitoring mode with a total run time of 4min. The method was validated in tissue homogenates with a daily working range of 1-1000ng/mL with correlation coefficient of more than 0.99 and a sensitivity of 1ng/mL as lower limit of quantification, respectively. The mean intra-day and inter-day precisions were less than 10% and accuracy values were higher than 90%. This method was fully validated for the accuracy, precision and stability studies. The method proved to be accurate and specific, and was applied to an in vivo biodistribution study of TA after intravitreal injection to rabbits. Values of mean residence time in vitreous humor, crystalline lens and aqueous humor were 27.7, 35.8 and 20.0 days, respectively. © 2011 Elsevier B.V.


The vaccinia virus Guang9 strain (VG9), derived from the vaccinia virus Tian Tan strain (VTT) has been found to be less virulent than VTT. To investigate whether VG9 could be a potential replicating virus vector, the TK genes in VG9 and VTT were replaced with the HIV-1 envelope gene via homologous recombination, resulting in the recombinant viruses, VG9-E and VTT-E. The biology, virulence, humoral and cellular immunological responses of VG9-E and VTT-E were evaluated. Our results indicated no obvious difference in range of host cells and diffusion between two recombinant viruses. Neurovirulence for VG9-E in weanling and suckling mice, and skin virulence in rabbits, were lower than that of VTT-E. The humoral immune responses, including binding antibody and neutralizing antibody responses, induced by VG9-E were not significantly different from those for VTT-E whilst IFN-γ response which represented cellular immune response induced by VG9-E was significantly higher than that did by VTT-E. Our results indicated that VG9-E was less virulent, yet induced higher cellular immune response than VTT-E. Therefore, it could be an ideal replicating vaccinia vector for HIV vaccine research and development.

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