Ru Bai

National Center for Nanoscience and Technology, Peping, Beijing, China

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Publications (16)92.85 Total impact

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    ABSTRACT: A number of studies have demonstrated that MWCNTs induce granuloma formation and fibrotic responses in vivo, and it has been recently reported that MWCNT-induced macrophage activation and subsequent TGF-β secretion contribute to pulmonary fibrotic responses. However, their direct effects against alveolar type-II epithelial cells and fibroblasts and the corresponding underlying mechanisms remain largely unaddressed. Here, MWCNTs are reported to be able to directly promote fibroblast-to-myofibroblast conversion and the epithelial-mesenchymal transition (EMT) through the activation of the TGF-β/Smad signaling pathway. Both of the cell transitions may play important roles in MWCNT-induced pulmonary fibrosis. Firstly, in-vivo and in-vitro data show that long MWCNTs can directly interact with fibroblasts and epithelial cells, and some of them may be uptaken into fibroblasts and epithelial cells by endocytosis. Secondly, long MWCNTs can directly activate fibroblasts and increase both the basal and TGF-β1-induced expression of the fibroblast-specific protein-1, α-smooth muscle actin, and collagen III. Finally, MWCNTs can induce the EMT through the activation of TGF-β/Smad2 signaling in alveolar type-II epithelial cells, from which some fibroblasts involved in pulmonary fibrosis are thought to originate. These observations suggest that the activation of the TGF-β/Smad2 signaling plays a critical role in the process of the fibroblast-to-myofibroblast transition and the EMT induced by MWCNTs.
    Small (Weinheim an der Bergstrasse, Germany). 09/2014;
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    ABSTRACT: Coronaviruses belong to the family Coronaviridae, which primarily cause infection of the upper respiratory and gastrointestinal tract of hosts. Transmissible gastroenteritis virus (TGEV) is an economically significant coronavirus that can cause severe diarrhea in pigs. Silver nanomaterials (Ag NMs) have attracted great interests in recent years due to their excellent anti-microorganism properties. Herein, four representative Ag NMs including spherical Ag nanoparticles (Ag NPs, NM-300), two kinds of silver nanowires (XFJ011) and silver colloids (XFJ04) were selected to study their inhibitory effect on TGEV-induced host cell infection in vitro. Ag NPs were uniformly distributed, with particle sizes less than 20 nm by characterization of environmental scanning electron microscope and transmission electron microscope. Two types of silver nanowires were 60 nm and 400 nm in diameter, respectively. The average diameter of the silver colloids was approximately 10 nm. TGEV infection induced the occurring of apoptosis in swine testicle (ST) cells, down-regulated the expression of Bcl-2, up-regulated the expression of Bax, altered mitochondrial membrane potential, activated p38 MAPK signal pathway, and increased expression of p53 as evidenced by immunofluorescence assays, real-time PCR, flow cytometry and Western blot. Under non-toxic concentrations, Ag NPs and silver nanowires significantly diminished the infectivity of TGEV in ST cells. Moreover, further results showed that Ag NPs and silver nanowires decreased the number of apoptotic cells induced by TGEV through regulating p38/mitochondria-caspase-3 signaling pathway. Our data indicate that Ag NMs are effective in prevention of TGEV-mediated cell infection as a virucidal agent or as an inhibitor of viral entry and the present findings may provide new insights into antiviral therapy of coronaviruses.
    Biomaterials 02/2014; · 8.31 Impact Factor
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    ABSTRACT: Zinc oxide nanoparticles (ZnO NPs) have been widely used in cosmetics and sunscreens, advanced textiles, self-charging and electronic devices, the potential for human exposure and the health impact at each stage of their manufacture and use is attracting great concerns. In addition to pulmonary damage, nanoparticle exposure is also strongly correlated with the increase in incidences of cardiovascular diseases, however, their toxic potential remains largely unclear. Herein, we investigated the cellular responses and endoplasmatic reticulum (ER) stress induced by ZnO NPs in human umbilical vein endothelial cells (HUVECs) in comparison with the Zn2+ ions and CeO2 NPs. We found that the dissolved zinc ion was the most significant factor for cytotoxicity in HUVECs. More importantly, ZnO NPs at non-cytotoxic concentration, but not CeO2 NPs, can induce significant cellular ER stress response with higher expression of spliced xbp-1, chop and caspase-12 at the mRNA level, and associated ER marker proteins including BiP, Chop, GADD34, p-PERK, p-eIF2α and cleaved Caspase-12 at the protein levels. Moreover, ER stress was widely activated after treatment with ZnO NPs, while six of 84 marker genes significantly increased. ER stress response is a sensitive marker for checking the interruption of ER homeostasis by ZnO NPs. Furthermore, higher dosage of ZnO NPs (240 μM) quickly rendered ER stress response before inducing apoptosis. These results demonstrate that ZnO NPs activate ER stress-responsive pathway and the ER stress response might be used as an earlier and sensitive endpoint for nanotoxicological study.
    ACS Nano 02/2014; · 12.03 Impact Factor
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    ABSTRACT: Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing attention. In this paper, integrated analytical techniques with high sensitivity were used to study the brain translocation and potential impairment induced by intranasally instilled copper nanoparticles (CuNPs). Mice were exposed to CuNPs in three doses (1, 10, 40 mg/kg bw). The body weight of mice decreased significantly in the 10 and 40 mg/kg group (p < 0.05) but recovered slightly within exposure duration. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that CuNPs could enter the brain. Altered distribution of some important metal elements were observed by synchrotron radiation X-ray fluorescence (SRXRF). H&E Staining and immunohistochemical analysis showed that CuNPs produced damages to nerve cells and astrocyte might be the one of the potential targets of CuNPs. The changes of neurotransmitter levels in different brain regions demonstrate that the dysfunction occurred in exposed groups. These data indicated that CuNPs could enter the brain after nasal inhalation and induced damages to the central nervous system (CNS). Integration of effective analytical techniques for systematic investigations is a promising direction to better understand the biological activities of nanomaterials.
    Toxicology Letters 01/2014; · 3.15 Impact Factor
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    ABSTRACT: We investigated how surface chemistry influences the interaction between gold nanorods (AuNRs) and cell membranes and the subsequent cytotoxicity arising from them in a serum-free cell culture system. Our results showed that the AuNRs coated with cetyl trimethylammonium bromide (CTAB) molecules can generate defects in the cell membrane and induce cell death, mainly due to the unique bilayer structure of CTAB molecules on the surface of the rods rather than their charge. Compared to CTAB-capped nanorods, positively charged polyelectrolyte-coated, i.e. poly(diallyldimethyl ammonium chloride) (PDDAC), AuNRs show improved biocompatibility towards cells. Thus, the present results indicate that the nature of surface molecules, especially their packing structures on the surface of AuNRs rather than surface charge, play a more crucial role in determining cytotoxicity. These findings about interfacial interactions could also explain the effects of internalized AuNRs on the structures or functions of organelles. This study will help understanding of the toxic nature of AuNRs and guide rational design of the surface chemistry of AuNRs for good biocompatibility in pharmaceutical therapy.
    Nanoscale 07/2013; · 6.73 Impact Factor
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    ABSTRACT: Multiwall carbon nanotubes (MWCNTs) have been widely used in many disciplines due to their unique physical and chemical properties, but have also raised great concerns about their possible negative health impacts, especially through occupational exposure. Although recent studies have demonstrated that MWCNTs induce granuloma formation and/or fibrotic responses in the lungs of rats or mice, their cellular and molecular mechanisms remain largely unaddressed. Here, it is reported that the TGF-β/Smad signaling pathway can be activated by MWCNTs and play a critical role in MWCNT-induced pulmonary fibrosis. Firstly, in vivo data show that spontaneously hypertensive (SH) rats administered long MWCNTs (20-50 μm) but not short MWCNTs (0.5-2 μm) exhibit increased fibroblast proliferation, collagen deposition and granuloma formation in lung tissue. Secondly, the in vivo experiments also indicate that only long MWCNTs can significantly activate macrophages and increase the production of transforming growth factor (TGF)-β1, which induces the phosphorylation of Smad2 and then the expression of collagen I/III and extracellular matrix (ECM) protease inhibitors in lung tissues. Finally, the present in vitro studies further demonstrate that the TGF-β/Smad signaling pathway is indeed necessary for the expression of collagen III in fibroblast cells. Together, these data demonstrate that MWCNTs stimulate pulmonary fibrotic responses such as fibroblast proliferation and collagen deposition in a TGF-β/Smad-dependent manner. These observations also suggest that tube length acts as an important factor in MWCNT-induced macrophage activation and subsequent TGF-β1 secretion. These in vivo and in vitro studies further highlight the potential adverse health effects that may occur following MWCNT exposure and provide a better understanding of the cellular and molecular mechanisms by which MWCNTs induce pulmonary fibrotic reactions.
    Small 05/2013; · 7.82 Impact Factor
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    ABSTRACT: Numerous unique properties of carbon nanotubes make them attractive for applications in neurobiology such as drug delivery, tissue regeneration, and as scaffolds for neuronal growth. In this study, the critical roles of the length of multiwall carbon nanotubes (MWCNTs) on a neuronal-like model cell line PC12 cells are investiaged. Incubation of PC12 cells with carboxylated MWCNTs did not significantly affect cellular morphology and viability at lower concentrations. Short MWCNTs show higher cellular uptake and more obvious removal compared to longer ones, which can result in higher ability to promote PC12 cell differentiation. Pre-incubation of short MWCNTs can up-regulate the expression of neurotrophin signaling pathway-associated TrkA/p75 receptors and Pincher/Gap43/TH proteins, which might be the underlying mechanism for the improved differentiation in PC12 cells. The current results provide insight for future applications of MWCNTs in neuron drug delivery and neurodegenerative disease treatment.
    Small 11/2012; · 7.82 Impact Factor
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    ABSTRACT: With more and more potential applications of carbon nanotubes (CNTs) in different fields, the risk of exposure to CNTs is increasing. The interaction between CNTs and protein in biological media can affect the way cells interact with, recognize and process the nanoparticles, and this has important implications for safety considerations. In this study, the interaction of single-walled and multiwall CNTs with various serum proteins was investigated. The adsorption kinetics of protein to CNTs was investigated and a semi-qualitative analysis was provided by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Matrix assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) was used to identify the protein species binding to CNTs and atomic force microscopy (AFM) was used to vividly demonstrate the adsorption model of protein on CNTs. All the experimental results showed that the adsorption capacity of CNTs for protein was highly dependent on the type, arrangement model, size and surface modification of CNTs. Significant quantity of proteins in serum could be quickly adsorbed by CNTs, mainly including albumin, prealbumin, transferrin, and immunoglobulin. Noncovalent functionalization of CNTs by polyethylene glycol (PEG) could decrease the protein adsorption on CNTs. These results provide crucial insights into human serum proteins binding to different kinds of CNTs, which is important for understanding the safe application of carbon nanotubes.
    Journal of Nanoscience and Nanotechnology 11/2011; 11(11):10102-10. · 1.15 Impact Factor
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    ABSTRACT: The rising commercial use and large-scale production of engineered nanoparticles (NPs) may lead to unintended exposure to humans. The central nervous system (CNS) is a potential susceptible target of the inhaled NPs, but so far the amount of studies on this aspect is limited. Here, we focus on the potential neurological lesion in the brain induced by the intranasally instilled titanium dioxide (TiO₂) particles in rutile phase and of various sizes and surface coatings. Female mice were intranasally instilled with four different types of TiO₂ particles (i.e. two types of hydrophobic particles in micro- and nano-sized without coating and two types of water-soluble hydrophilic nano-sized particles with silica surface coating) every other day for 30 days. Inductively coupled plasma mass spectrometry (ICP-MS) were used to determine the titanium contents in the sub-brain regions. Then, the pathological examination of brain tissues and measurements of the monoamine neurotransmitter levels in the sub-brain regions were performed. We found significant up-regulation of Ti contents in the cerebral cortex and striatum after intranasal instillation of hydrophilic TiO₂ NPs. Moreover, TiO₂ NPs exposure, in particular the hydrophilic NPs, caused obvious morphological changes of neurons in the cerebral cortex and significant disturbance of the monoamine neurotransmitter levels in the sub-brain regions studied. Thus, our results indicate that the surface modification of the NPs plays an important role on their effects on the brain. In addition, the difference in neurotoxicity of the two types of hydrophilic NPs may be induced by the shape differences of the materials. The present results suggest that physicochemical properties like size, shape and surface modification of the nanomaterials should be considered when evaluating their neurological effects.
    Toxicology Letters 08/2011; 207(1):73-81. · 3.15 Impact Factor
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    ABSTRACT: The fate of nanomaterials with different sizes and charges in mitotic cells is of great importance but seldom explored. Herein we investigate the intracellular fate of negatively charged carboxylated polystyrene (COOH-PS) and positively charged amino-modified polystyrene (NH(2)-PS) nanoparticles of three different diameters (50, 100 and 500 nm) on cancer HeLa cells and normal NIH 3T3 cells during the cell cycles. The results showed that all the fluorescent PS nanoparticles differing in size and/or charge did not interact with chromosome reorganization and cytoskeleton assembly during the mitotic process in live cells. They neither disturbed chromosome reorganization nor affected the cytoskeleton reassembly in both normal and cancer cells. However, NH(2)-PS at the size of 50 nm caused G1 phase delay and a decrease of cyclin (D, E) expression, respectively. Moreover, NH(2)-PS displayed higher cellular toxicity and NH(2)-PS of 50 nm disturbed the integrity of cell membranes. Both cationic and anionic PS nanoparticles had a more pronounced effect on normal NIH 3T3 cells than cancer HeLa cell. Our research provides insight into the dynamic fate, intracellular behavior, and the effects of nanoparticles on spindle and chromosomes during cell division, which will enable the optimization of design and selection of much safer nanoparticles for lower risk to human health and widely medical applications.
    Biomaterials 07/2011; 32(32):8291-303. · 8.31 Impact Factor
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    ABSTRACT: Increasing production and application of metallic nanomaterials are likely to result in the release of these particles into the environment. These released nanoparticles may enter into the lungs and the central nervous system (CNS) directly through inhalation, which therefore poses a potential risk to human health. Herein, we focus on the systemic toxicity and potential influence on the neurotransmitter secretion of intranasally instilled copper nanoparticles (23.5 nm) at three different doses. Copper nanoparticle-exposed mice exhibit pathological lesions at different degrees in certain tissues and especially in lung tissue as revealed by histopathology and transmission electron microscopy (TEM) observations. Inductively-coupled plasma mass spectrometry (ICP-MS) results show that the liver, lung and olfactory bulb are the main tissues in which the copper concentrations increased significantly after exposure to a higher level of Cu nanoparticles (40 mg/kg of body weight). The secretion levels of various neurotransmitters changed as well in some brain regions, especially in the olfactory bulb. Our results indicate that the intranasally instilled copper nanoparticles not only cause the lesions where the copper accumulates, but also affect the neurotransmitter levels in the brain.
    Nanotoxicology 06/2011; 6(5):562-75. · 7.84 Impact Factor
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    ABSTRACT: As a novel kind of nanomaterial with wide potential applications, the adverse effects of carbon nanotubes (CNTs) have recently received significant attention after respiratory exposure. In this study, single-wall carbon nanotubes (SWCNTs) containing different metal contents were intratracheally instilled into lungs of spontaneously hypertensive rats. Pulmonary and cardiovascular system alterations were evaluated at 24 and 72 h post-instillation. Biomarkers of inflammation, oxidative stress and cell damage in the bronchoalveolar lavage fluid (BALF) were increased significantly 24 h post-exposure of SWCNTs. The increased endothelin-1 levels in BALF and plasma and angiotensin I-converting enzyme in plasma suggested endothelial dysfunction in the pulmonary circulation and peripheral vascular thrombosis. These findings suggest that respiratory exposure to SWCNTs can induce acute pulmonary and cardiovascular responses and individuals with existing cardiovascular diseases are very susceptible to SWCNTs exposure. The co-existence of metal residues in SWCNTs can aggravate the adverse effects.
    Nanotoxicology 06/2011; 6(5):526-42. · 7.84 Impact Factor
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    ABSTRACT: Gold nanorods (Au NRs) have been recognized as promising materials for biomedical applications, like sensing, imaging, gene and drug delivery and therapy, but their toxicological issues are still controversial, especially for the Au NRs synthesized with seed-mediated method. In this study, we investigated the influence of aspect ratio and surface coating on their toxicity and cellular uptake. The cellular uptake is highly dependent on the aspect ratio and surface coating. However, the surface chemistry has the dominant roles since PDDAC-coated Au NRs exhibit a much greater ability to be internalized by the cells. The present data demonstrated shape-independent but coating-dependent cytotoxicity. Both the CTAB molecules left in the suspended solution and on the surface of Au NRs were identified as the actual cause of cytotoxicity. CTAB can enter cells with or without Au NRs, damage mitochondria, and then induce apoptosis. The effects of surface coating upon toxicity and cellular uptake were also examined using Au NRs with different coatings. When Au NRs were added into the medium, the proteins were quickly adsorbed onto the Au NRs that made the surface negatively charged. The surface charge may not directly affect the cellular uptake. We further demonstrated that the amount of serum proteins, especially for BSA, adsorbed on the Au NRs had a positive correlation with the capacity of Au NRs to enter cells. In addition, we have successfully revealed that the cationic PDDAC-coated Au NRs with an aspect ratio of 4 possess an ideal combination of both negligible toxicity and high cellular uptake efficiency, showing a great promise as photothermal therapeutic agents.
    Biomaterials 10/2010; 31(30):7606-19. · 8.31 Impact Factor
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    ABSTRACT: The release of ultrafine particles from office equipment is currently receiving great concerns due to its potential threat to human health when inhaled. Printer toner is one of the largest consumables in daily office work, and the particles released from printers and photocopiers may pose damage to respiratory system. In this study, we found the particles can be released into the surrounding environment during the printing process and the concentrations of PM(2.5) and PM(10) particles increased obviously. To evaluate the time-course pulmonary responses caused by toner particles, the toner suspension was instilled into the lungs of the male mice through intratracheally instillation every other day for four times and the pulmonary responses of the lung were monitored at days 9, 28, 56 and 84. Indeed, mice treated with toner particles displayed a slower body weight growth rate during the recovery phase. The total cell number in bronchoalveolar lavage fluids (BALF) of toner-exposed groups was much higher than the saline-treated groups. The total protein, lactate dehydrogenase and acid phosphatase in BALF exhibited significant changes (p<0.05 or p<0.01) at different time points. The nitric oxide synthase, interleukin 1-beta, and interleukin 6 in the lung tissue of the toner-exposed groups also exhibited significant changes (p<0.05 or p<0.01). The pathological examination showed that toner particles can adhere to the alveolar septal walls, then enter into the alveoli and cause pulmonary lesion. During the experimental period, particles phagocytosed by alveolar macrophages (AMs) led to an increase of both AMs number and apoptosis. The pulmonary stress still remained over time even with a clearance period for 12 weeks. These results indicate that exposure to toner particles can inhibit the normal growth of the mice and induce significant inflammatory responses and lesion in the lung tissues. The health and safety effects from working indoors in offices with fumes and particles released from photocopiers and printers need to be paid more attention.
    Toxicology Letters 09/2010; 199(3):288-300. · 3.15 Impact Factor
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    ABSTRACT: With the rapid development of nanotechnology, the presence of nanoparticles (NPs) in commercially available products is becoming more and more common. The field of food nanotechnology has experienced significant growth over the last five years. Agricultural cultivation, food processing, food packaging, food security, and water purification are examples of the important sectors linked with nanotechnology in the food production chain. However, safety concerns about such nanotechnology and the use of nanomaterials are increasing. Many determinants for the unusual activities and toxicities of the nanomaterials involving particle size, chemical composition, surface structure, and dosage are considered as well as three main exposure routes, including inhalation, ingestion, and dermal exposure. In addition, the trends and progress for toxicity and risk evaluation of the nanomaterials used in the food industry are also reviewed, which are helpful to understand and establish a regulatory system for the further development and use of NPs in the food industry.
    Pure and Applied Chemistry 01/2010; 82(2):349-372. · 3.39 Impact Factor
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    ABSTRACT: Publications concerning the mechanism of biological activity, especially the immunological mechanism of C(60)(OH)(20) nanoparticles, are relatively limited. However, the structure and characteristics of this carbon allotrope have been widely investigated. In this paper, we have demonstrated that water-soluble C(60)(OH)(20) nanoparticles have an efficient anti-tumor activity in vivo, and show specific immunomodulatory effects to the immune cells, such as T cells and macrophages, both in vivo and in vitro. For example, C(60)(OH)(20) nanoparticles can increase the production of T-helper cell type 1 (Th1) cytokines (IL-2, IFN- gamma and TNF-alpha), and decrease the production of Th2 cytokines (IL-4, IL-5 and IL-6) in serum samples. On the other hand, C(60)(OH)(20) nanoparticles show almost no adverse effect to the viability of immune cells in vitro but stimulate the immune cells to release more cytokines, in particular TNF- alpha, which plays a key role in the cellular immune process to help eliminate abnormal cells. TNF- alpha production increased almost three-fold in treated T lymphocytes and macrophages. Accordingly, we conclude that C(60)(OH)(20) nanoparticles have an efficient anti-tumor activity and this effect is associated with an increased CD(4)(+)/CD(8)(+) lymphocyte ratio and the enhancement of TNF- alpha production. The data suggest that C(60)(OH)(20) nanoparticles can improve the immune response to help to scavenge and kill tumor cells.
    Nanotechnology 10/2009; 20(41):415102. · 3.84 Impact Factor

Publication Stats

187 Citations
92.85 Total Impact Points


  • 2009–2013
    • National Center for Nanoscience and Technology
      Peping, Beijing, China
    • Northeast Institute of Geography and Agroecology
      • Key Laboratory of Nuclear Analytical Techniques
      Beijing, Beijing Shi, China
  • 2011
    • University of South China
      Heng-nan, Hunan, China