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Biomedical subjects

Z Cai

Publications and source records attributed to Z Cai.

At least 19 recordsLinked to original sources

Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells.

Antigen-presenting cells such as dendritic cells (DCs) play a critical role in inducing and regulating immune responses. One effective strategy for DC-based immunotherapy is to regulate maturation and function of DC. In this study, we apply single-walled carbon nanotubes (SWNTs) to carry small interfering RNA (siRNA) to reach, enter and genetically modify DCs in vivo. We prepared positively charged SWNTs (SWNTs+) using 1,6-diaminohexane which was demonstrated by transmission electron microscopy equipped with energy-dispersive X-ray spectroscopy and atomic force microscope. The functionalized SWNTs+ could absorb siRNA to form complexes of siRNA with SWNTs. These siRNA:SWNT+ complexes were preferentially taken up by splenic CD11c+ DCs, CD11b+ cells and also Gr-1+CD11b+ cells comprising DCs, macrophages and other myeloid cells to silence the targeting gene. Suppressor of cytokine signaling 1 (SOCS1) restricts the ability of DCs to break self-tolerance and induce antitumor immunity. Infusion of SWNTs+ carrying SOCS1siRNA reduced SOCS1 expression and retarded the growth of established B16 tumor in mice, indicating the possibility of in vivo immunotherapeutics using SWNTs-based siRNA transfer system.

Animals↗

Role of interleukin-6 in lipopolysaccharide-induced brain injury and behavioral dysfunction in neonatal rats.

There are increasing data in support of the hypothesis that inflammatory cytokines are involved in neonatal white matter damage. Despite extensive study of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta, the role of interleukin-6 in the development of white matter damage is largely unknown. In the present study, the role(s) of interleukin-6 in mediating lipopolysaccharide-induced brain injury and behavioral changes was investigated by the intracerebral injection of lipopolysaccharide with interleukin-6 neutralizing antibody in the 5-day-old rat brain. Brain injury was examined in brain sections at postnatal day 8 and postnatal day 21. Behavioral tests including righting reflex, wire hanging maneuver, cliff avoidance, locomotor activity, gait analysis, responses in the elevated plus-maze and passive avoidance were performed from postnatal day 3 to postnatal day 21. Changes in astroglia, microglia and oligodendrocytes were studied using immunohistochemistry in the postnatal day 21 rat brain. Our results show that interleukin-6 antibody attenuated lipopolysaccharide-induced brain lateral ventricle dilation and improved neurobehavioral performance. Interleukin-6 antibody also suppressed lipopolysaccharide-induced astrogliosis and microglial activation, and increased the number of oligodendrocytes in white matter. However, no changes of tumor necrosis factor-alpha and interleukin-1beta were detected. In contrast, no histopathological changes and glial activation were observed in rats injected with only interleukin-6. The present study indicates that the contribution to brain injury by interleukin-6 depends on its interaction with other lipopolysaccharide-induced agents and not on interleukin-6 alone.

Age Factors↗

Shear modulus and plasticity of a driven charge density wave.

We have probed the effects of transverse variations in pinning strength on charge-density-wave (CDW) structure in NbSe3 by x-ray micro-beam diffraction. In ribbonlike crystals having a large longitudinal step in thickness, the CDW first depins on the thick side of the step, causing rotations of the CDW wave vector. By measuring these rotations as a function of position and electric field, the corresponding shear strains are determined, allowing the CDW's shear modulus to be estimated. These results demonstrate the usefulness of x-ray microdiffraction as a tool in studying collective dynamics in electronic crystals.

Journal Article↗

Paranodal pathology in Tangier disease with remitting-relapsing multifocal neuropathy.

Pathological studies of a sural nerve biopsy in a man with Tangier disease presenting as a remitting-relapsing multifocal neuropathy showed abnormalities in the paranodal regions, including lipid deposition (65%) and redundant myelin foldings, with various degrees of myelin splitting and vesiculation (43%) forming small tomacula and abnormal myelin terminal loops (4%). The internodal regions were normal in the majority of myelinated fibres. Abnormal lipid storage was also present in the Schwann cells of the majority of unmyelinated fibres (67%). The evidence suggests that the noncompacted myelin region of the paranode is a preferential site for lipid storage in the myelinated Schwann cell, and that the space-occupying effects of the cholesterol esters leads to paranodal malfunction and tomacula formation as the pathological basis for the multifocal relapsing-remitting clinical course.

Adolescent↗

Avian riboflavin deficiency: an acquired tomaculous neuropathy.

The finding of tomacula, focal areas of sausage-shaped hypermyelination in peripheral nerves, is reported for the first time in avian riboflavin deficiency. Day-old, meat-type chickens were fed a riboflavin-deficient diet (1.8 mg/kg) and were killed on postnatal days 6, 11, 16, and 21, while control chickens were fed a conventional diet containing 5.0 mg/kg riboflavin. Tomacula were found in sciatic and brachial nerves from day 11 onward, became more frequent and prominent with increasing time, and preceded the onset of segmental demyelination.

Animal Feed↗

Early paranodal myelin swellings (tomacula) in an avian riboflavin deficiency model of demyelinating neuropathy.

INTRODUCTION: Disruption of the complex architectural and molecular organization of the paranodal region of myelinated peripheral nerve fiber may initiate the evolving time dependent process of segmental demyelination. In support of this notion was the finding of focal paranodal myelin swellings (tomacula) due to redundant folding of myelin sheaths, early in the time course of an avian riboflavin deficiency model of demyelinating neuropathy. METHODS: Newborn broiler meat chickens were maintained either on a routine diet containing 5.0 mg/kg riboflavin (control group) or a riboflavin-deficient diet containing 1.8 mg/kg riboflavin. Riboflavin concentrations in the liver were measured at postnatal day 11. Peripheral nerves were morphologically examined at days 6, 11, 16 and 21 using light and electron microscopy and teased nerve fiber techniques. RESULTS: Riboflavin-deficient chickens showed signs of a neuropathy from days 8 and pathological examination of peripheral nerves revealed a demyelinating neuropathy with paranodal tomacula formation starting on day 11. Paranodal tomacula consisted of redundant myelin infoldings or outfoldings, increased in size and frequency after day 11. After day 16, the paranodal swellings showed prominent degenerative changes accompanied by an increased frequency of myelinated fibers showing demyelination. CONCLUSION: Tomacula due to redundant myelin folds are generally considered a remyelination phenomenon, yet in this avian riboflavin deficiency model of demyelination, the paranodal tomacula occurred early in the course of demyelination.

Animals↗

Minocycline alleviates hypoxic-ischemic injury to developing oligodendrocytes in the neonatal rat brain.

The role of minocycline in preventing white matter injury, in particular the injury to developing oligodendrocytes was examined in a neonatal rat model of hypoxia-ischemia. Hypoxia-ischemia was achieved through bilateral carotid artery occlusion followed by exposure to hypoxia (8% oxygen) for 15 min in postnatal day 4 Sprague-Dawley rats. A sham operation was performed in control rats. Minocycline (45 mg/kg) or normal phosphate-buffered saline was administered intraperitoneally 12 h before and immediately after bilateral carotid artery occlusion+hypoxia and then every 24 h for 3 days. Nissl staining revealed pyknotic cells in the white matter area of the rat brain 1 and 5 days after hypoxia-ischemia. Hypoxia-ischemia insult also resulted in apoptotic oligodendrocyte cell death, loss of O4+ and O1+ oligodendrocyte immunoreactivity, and hypomyelination as indicated by decreased myelin basic protein immunostaining and by loss of mature oligodendrocytes in the rat brain. Minocycline significantly attenuated hypoxia-ischemia-induced brain injury. The protective effect of minocycline was associated with suppression of hypoxia-ischemia-induced microglial activation as indicated by the decreased number of activated microglia, which were also interleukin-1beta and inducible nitric oxide synthase expressing cells. The protective effect of minocycline was also linked with reduction in hypoxia-ischemia-induced oxidative and nitrosative stress as indicated by 4-hydroxynonenal and nitrotyrosine positive oligodendrocytes, respectively. The reduction in hypoxia-ischemia-induced oxidative stress was also evidenced by the decreases in the content of 8-isoprostane in the minocycline-treated hypoxia-ischemia rat brain as compared with that in the vehicle-treated hypoxia-ischemia rat brain. The overall results suggest that reduction in microglial activation may protect developing oligodendrocytes in the neonatal brain from hypoxia-ischemia injury.

Animals↗

Identification of a novel insulin-like growth factor binding protein gene homologue with tumor suppressor like properties.

Here we report the identification of a new insulin-like growth factor binding protein homologue, provisionally designated insulin-like growth factor binding related protein-4 (IGFBP-rP4). IGFBP-rP4 was found to be most closely related to IGFBP-7 with 52% amino acid homology and 43% amino acid identity, and shares a similar domain structure. Semi-quantitative RT-PCR expression analysis demonstrated a pattern of downregulation of this gene in multiple tumor samples including lung and colon cancer, compared to matched adjacent normal tissue. Western blotting revealed a protein of approximately 38kDa expressed in both the cell pellet and secreted into the supernatant of transiently transfected Cos-7 cells. Cos-7 supernatants containing IGFBP-RP4 protein were observed to suppress the growth of HeLa cells in culture compared to vector controls. IGFBP-RP4 directly transiently transfected into HeLa cells also further confirmed the growth suppressive properties of this protein. Together these data suggest that IGFBP-RP4 may be a novel putative tumor suppressor protein.

Amino Acid Sequence↗

Minocycline attenuates lipopolysaccharide-induced white matter injury in the neonatal rat brain.

Our previous studies have shown that intracerebral administration of endotoxin, lipopolysaccharide (LPS), induces selective white matter injury and hypomyelination in the neonatal rat brain and that the LPS-induced brain injury is associated with activation of microglia. To test the hypothesis that inhibition of microglial activation may protect against LPS-induced white matter injury, we examined roles of minocycline, a putative suppressor of microglial activation, on LPS-induced brain injury in the neonatal rat. A stereotactic intracerebral injection of LPS (1 mg/kg) was performed in postnatal day 5 Sprague-Dawley rats and control rats were injected with sterile saline. Minocycline (45 mg/kg) was administered intraperitoneally 12 h before and immediately after LPS injection and then every 24 h for 3 days. Inflammatory responses, activation of microglia and brain injury were examined 1 and 3 days after LPS injection. LPS injection resulted in brain injury in selective brain areas, including bilateral ventricular enlargement, cell death at the sub- and periventricular areas, loss of O4+ and O1+ oligodendrocyte (OL) immunoreactivity and hypomyelination, as indicated by decreased myelin basic protein immunostaining, in the neonatal rat brain. Minocycline administration significantly attenuated LPS-induced brain injury in these rat brains. The protective effect of minocycline was associated with suppressed microglial activation as indicated by the decreased number of activated microglial cells following LPS stimulation and with consequently decreased elevation of interleukin 1beta and tumor necrosis factor-alpha concentrations induced by LPS and a reduced number of inducible nitric oxide synthase expressing cells. Protection of minocycline was also linked with the reduction in LPS-induced oxidative stress, as indicated by 4-hydroxynonenal positive OLs. The overall results suggest that reduction in microglial activation may protect the neonatal brain from LPS-induced white matter injury and inhibition of microglial activation might be an effective approach for the therapeutic treatment of infection-induced white matter injury.

Animals↗

The ratios of individual chemicals in a mixture determine the degree of joint effect: the climax hypothesis.

A new hypothesis, the Climax Hypothesis, is proposed to describe how the ratios of individual chemicals influence the joint effects of chemical mixtures. This hypothesis is derived from a generalized approach using "isobolograms". With this hypothesis, one can predict that for a given mixture, a curvilinear correlation exists between the joint effects and the ratios of individual chemicals and that this curve has a climax at the equitoxic ratio. This prediction is supported by the observed toxicity to Vibrio fischeri of 18 mixtures (12 binary mixtures, 4 ternary mixtures, and 2 quaternary mixtures). With this prediction, the Climax Hypothesis has some promising applications such as controlling the discharge of effluents in environmental science, maximizing detoxifying effects in medicine, and optimizing combined pesticides in agriculture.

Data Interpretation, Statistical↗

Electrochemical characterization of cast Ti-Hf binary alloys.

This study characterized the electrochemical behavior of Ti-Hf binary alloys in a simulated oral environment. Ti-Hf alloys (10, 20, 25, 30, 35 and 40 mass% Hf) were prepared by arc-melting titanium sponge and hafnium sponge. Specimens of each alloy (n = 4) were prepared using a dental titanium casting system with a MgO-based investment. Specimens were inspected with X-ray radiography to ensure minimal internal porosity. Castings (n = 4) made from pure titanium and commercially pure titanium were used as controls. The ground flat surface (10 mm x 10 mm) on each specimen where approximately 30 microm was removed was used for the characterization. Sixteen-hour open-circuit potential (OCP) measurement, linear polarization and potentiodynamic cathodic polarization were performed sequentially in aerated (air + 10% CO2) MTZ synthetic saliva at 37 degrees C. Potentiodynamic anodic polarization was conducted in the same medium but deaerated (N2 + 10% CO2) 2 h before and during testing. Polarization resistance (R(P)) and Tafel slopes were determined, as were corrosion current density (I(CORR)) and passive current density (I(PASS)). Results were subjected to nonparametric statistical analysis (alpha = 0.05). The OCP stabilized (mean values -229 mV to -470 mV vs. SCE) for all specimens after the 16-h immersion. Similar passivation was observed for all the metals on their anodic polarization diagrams. The Kruskal-Wallis test showed significant differences in OCP among the test groups (p = 0.006). No significant differences were found in R(P), I(CORR) or I(PASS) among all the metals (p>0.3). Results indicate that the electrochemical behavior of the Ti-Hf alloys examined resembles that of pure titanium.

Alloys↗

An X-ray nanodiffraction technique for structural characterization of individual nanomaterials.

An X-ray micro/nanodiffraction technique that allows structural characterization of individual nanomaterials has been developed at an insertion-device beamline of the Advanced Photon Source. Using the extremely high brightness of the third-generation synchrotron radiation source and advanced high-resolution high-energy zone-plate focusing optics, X-rays of energies from 6 to 12 keV have been focused into a spot smaller than 200 nm with a photon density gain of more than 50,000 so that significant photon flux can be intercepted by a nanoscale material to generate a measurable diffraction signal for structural characterization. This paper describes the instrumentation of the technique and discusses the application of the technique to studies of tin oxide nanobelts.

Journal Article↗

Effect of cryogenic treatment on nickel-titanium endodontic instruments.

AIM: To investigate the effects of cryogenic treatment on nickel-titanium endodontic instruments. The null hypothesis was that cryogenic treatment would result in no changes in composition, microhardness or cutting efficiency of nickel-titanium instruments. METHODOLOGY: Microhardness was measured on 30 nickel-titanium K-files (ISO size 25) using a Vicker's indenter. Elemental composition was measured on two instruments using X-ray spectroscopy. A nickel-titanium bulk specimen was analysed for crystalline phase composition using X-ray diffraction. Half of the specimens to be used for each analysis were subjected to a cryogenic treatment in liquid nitrogen (-196 degrees C) for either 3 s (microhardness specimens) or 10 min (other specimens). Cutting efficiency was assessed by recording operator choice using 80 nickel-titanium rotary instruments (ProFile 20, .06) half of which had been cryogenically treated and had been distributed amongst 14 clinicians. After conditioning by preparing four corresponding canals, each pair of instruments were evaluated for cutting efficiency by a clinician during preparation of one canal system in vitro. A Student's t-test was used to analyse the microhardness data, and a binomial test was used to analyse the observer choice data. Composition data were analysed qualitatively. RESULTS: Cryogenically treated specimens had a significantly higher microhardness than the controls (P < 0.001; beta > 0.999). Observers showed a preference for cryogenically treated instruments (61%), but this was not significant (P = 0.21). Both treated and control specimens were composed of 56% Ni, 44% Ti, 0% N (by weight) with a majority in the austenite phase. CONCLUSIONS: Cryogenic treatment resulted in increased microhardness, but this increase was not detected clinically. There was no measurable change in elemental or crystalline phase composition.

Cold Temperature↗

SEM/EDS evaluation of porcelain adherence to gold-coated cast titanium.

The adhesion between titanium and dental porcelain is related to the diffusion of oxygen to the reaction layer formed on cast-titanium surfaces during porcelain firing. The diffusion of oxygen could be suppressed by coating the titanium surface with a thin gold layer. This study characterized the effects of gold coating on titanium-ceramic adhesion. ASTM grade II CP titanium was cast into a MgO-based investment (Selevest CB, Selec). The specimen surfaces were air abraded with 110-microm Al(2)O(3) particles. Gold coating was applied on titanium surfaces by three methods: gold-paste (Deck Gold NF, Degussa-Ney) coating and firing at 800 degrees C for three times, single gold-paste coating and firing followed by sputter coating (40 mA, 500 s), and sputter coating (40 mA, 1000 s). Surfaces only air abraded with Al(2)O(3) particles were used as controls. An ultra-low-fusing dental porcelain (Vita Titankeramik, Vident) was fused on titanium surfaces. Specimen surfaces were characterized by SEM/EDS and XRD. The titanium-ceramic adhesion was evaluated by a biaxial flexure test (N = 8), and area fraction of adherent porcelain (AFAP) was determined by EDS. Numerical results were statistically analyzed by one-way ANOVA and the Student-Newman-Keuls test at alpha = 0.05. SEM fractography showed a substantial amount of porcelains remaining on the gold-sputter-coated titanium surfaces. A new Au(2)Ti phase was found on gold-coated titanium surface after the firing. Significantly higher (p <.05) AFAP values were determined for the gold-sputter-coated specimens compared to the others. No significant differences were found among the other groups and the control. Results suggested that gold coatings used in this study are not effective barriers to completely protect titanium from oxidation during the porcelain firing, and porcelain adherence to cast titanium can be improved by gold-sputter coating used in the present study.

Dental Porcelain↗

Prevention of murine acute graft-versus-host disease by recipient-derived TGFbeta1-treated dendritic cells.

Acute graft-versus-host disease (GVHD) remains the major barrier to allogeneic bone marrow transplantation (allo-BMT). Evidence has accumulated that transforming growth factor beta1-treated dendritic cells (TGFbeta-DC), deficient in surface costimulatory molecules, inhibit alloantigen-specific T-cell responses and induce graft hyporeactivity. To analyze the effect of TGFbeta-DC on GVHD after allo-BMT, 5.0 x 10(6) recipient-derived TGFbeta-DC were injected into C57BL/6 (H-2b) with bone marrow-splenocyte grafts from major histocompatibility complex (MHC) disparate BALB/c mice (H-2d). Survival analysis showed TGFbeta-DC cotransplantation resulted in significant prolongation of allograft survival, namely a mean survival time (MST) of 44.3 +/- 4.5 days, versus the untreated MST of 9.5 +/- 0.6 days (P < .01). However, mature DC aggravated the GVHD with an MST of 6.6 +/- 0.6 days (P < .01). In addition, the third-party C3H-derived TGFbeta-DC did not enhance the survival rate (MST = 9.7 +/- 0.5 days). Furthermore, serum IFN-gamma, IL-12, and IL-18 levels in TGFbeta-DC cotransplanted mice were reduced compared with untreated BMT hosts, while serum IL-10 levels were not changed. These results suggest that TGFbeta-DC cotransplantation may attenuate the severity of GVHD after BMT.

Animals↗

Leaching from solid waste incineration ashes used in cement-treated base layers for pavements.

Waste incineration bottom ash and treated flue gas cleaning products mixed with 2.5% of cement (50 kg/m3) were tested in the laboratory in terms of compressive strength and tank leaching tests over a 64-day period. Although the material displayed lower mechanical strength than a reference concrete, the strength still was sufficient for use as a base layer for roads. The metal content in the incineration-residue-based specimens was up to 100 times higher than in the reference concrete, suggesting that the mixed waste incineration residue should be used only for dedicated purposes. The leaching of Cl and Na was increased by a factor of 20-100 from the incineration-residue-based specimens as compared to the reference, while the leaching of K, Ca and SO4 was increased by a factor of 2-10. The leaching of heavy metals was also higher from the incineration-residue-based specimens than from the reference with respect to Cu (50 times), Cd, Pb and Zn (5 times), but not with respect to Cr and Ni. The leaching curves did only allow for a closer evaluation of the leaching process in a few cases. The physical retention of the constituents seemed to be the same in the reference as in the incineration-residue-based specimens. Heavy metal leaching was limited by enhanced chemical retention in the incineration-residue-specimens as compared to the reference. Since no quality criteria in terms of leaching from a monolithic material are currently available, the leaching issue must be evaluated case by case.

Carbon↗

Cytotoxicity of commercial and novel binary titanium alloys with and without a surface-reaction layer.

Titanium-based alloys form a surface reaction layer when cast. This study investigated the effect of the surface reaction layer on the cytotoxicity of novel Ti-based binary alloys. The cytotoxicities of the novel alloys were compared with commercially pure titanium, Ti-6Al-4V and Ti-6Al-7Nb. Cast discs with or without the reaction layer were first tested for cytotoxicity, then for elemental release into cell-culture medium. The elements released into the extracts were measured by means of an inductively coupled plasma atomic emission spectrometer. The commercial and novel binary Ti-based alloys showed no statistically significant cytotoxicity, although some trends were noted for several alloys. The presence of the reaction layer did not significantly alter the cytotoxicity. These favourable biocompatibility results show that these novel alloys have promise for use in dental restorations.

Alloys↗