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Find video protocols related to scientific articles indexed in Pubmed.
In vivo fluorescence sensing of the salicylate-induced change of zinc ion concentration in the auditory cortex of rat brain.
Analyst
PUBLISHED: 10-10-2014
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This study demonstrates a fluorescence method for in vivo sensing of the dynamic change of Zn(2+) concentration in auditory cortex microdialysates induced by salicylate with N'-(7-nitro-2,1,3-benzoxadiazole-4-yl)-N,N,N'-tris(pyridine-2-ylmethyl) ethane-1,2-diamine (NBD-TPEA) as a probe. The excellent properties of the NBD-TPEA probe make it possible to achieve a high selectivity for Zn(2+) sensing with the co-existence of amino acids and other metal ions as well as the species commonly existing in the cerebral system. To validate the method for in vivo fluorescence sensing of Zn(2+) in the rat brain, we pre-mix the microdialysates in vivo sampled from the auditory cortex with the NBD-TPEA probe and then perfuse the mixtures into a fluorescent cuvette for continuous-flow fluorescence detection. The method demonstrated here shows a linear relationship between the signal output and Zn(2+) concentration within the concentration range from 0.5 ?M to 4 ?M, with a detection limit of 156 nM (S/N = 3). The basal level of extracellular Zn(2+) in auditory cortex microdialysates is determined to be 0.52 ± 0.082 ?M (n = 4). This value is increased by the injection of 100 mg mL(-1) of salicylate (1 ?L min(-1), 5 min, i.p.), reaches a peak at the time point of 90 min, and levels off with time. Such an increase is attenuated by the injection of MK-801, a potent and specific NMDA receptor antagonist, after the pre-injection of 100 mg mL(-1) salicylate for 5 min. This study offers a fluorescence method for in vivo sensing of Zn(2+) in the rat brain that could be useful for the investigations of chemical processes involved in brain functions.
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In vivo ratiometric Zn2+ imaging in zebrafish larvae using a new visible light excitable fluorescent sensor.
Chem. Commun. (Camb.)
PUBLISHED: 08-29-2014
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A visible light excitable ratiometric Zn(2+) sensor was developed by integrating a Zn(2+) chelator as the ICT donor of the fluorophore sulfamoylbenzoxadiazole, which displays the Zn(2+)-induced hypsochromic emission shift (40 nm) and favors the in vivo ratiometric Zn(2+) imaging in zebrafish larvae.
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Platinum(II)-Gadolinium(III) Complexes as Potential Single-Molecular Theranostic Agents for Cancer Treatment.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-01-2014
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Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3 )2 Cl}2 GdL](NO3 )2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (?0.1?mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1 -weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment.
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An H?O?-responsive nanocarrier for dual-release of platinum anticancer drugs and O?: controlled release and enhanced cytotoxicity against cisplatin resistant cancer cells.
Chem. Commun. (Camb.)
PUBLISHED: 07-15-2014
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Synergistic release of platinum anticancer drugs and O2 can be achieved in an H2O2-responsive nanocarrier incorporated with catalase. Such a system combines the advantages of chemotherapy and oxygen therapy and demonstrated improved therapeutic efficacy against cisplatin resistant cell lines which often appear to be in hypoxia.
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Using an instrumental variable to test for unmeasured confounding.
Stat Med
PUBLISHED: 05-05-2014
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An important concern in an observational study is whether or not there is unmeasured confounding, that is, unmeasured ways in which the treatment and control groups differ before treatment, which affect the outcome. We develop a test of whether there is unmeasured confounding when an instrumental variable (IV) is available. An IV is a variable that is independent of the unmeasured confounding and encourages a subject to take one treatment level versus another, while having no effect on the outcome beyond its encouragement of a certain treatment level. We show what types of unmeasured confounding can be tested for with an IV and develop a test for this type of unmeasured confounding that has correct type I error rate. We show that the widely used Durbin-Wu-Hausman test can have inflated type I error rates when there is treatment effect heterogeneity. Additionally, we show that our test provides more insight into the nature of the unmeasured confounding than the Durbin-Wu-Hausman test. We apply our test to an observational study of the effect of a premature infant being delivered in a high-level neonatal intensive care unit (one with mechanical assisted ventilation and high volume) versus a lower level unit, using the excess travel time a mother lives from the nearest high-level unit to the nearest lower-level unit as an IV.
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A turn-on fluorescent Fe(3+) sensor derived from an anthracene-bearing bisdiene macrocycle and its intracellular imaging application.
Chem. Commun. (Camb.)
PUBLISHED: 03-27-2014
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Integrating N(2)-hydroxyethyldiethylenetriamine with anthracene gives a [2+2] macrocycle fluorescent sensor. This sensor displays an instant/reversible turn-on response specific to Fe(3+), which allows facile visualization of the Fe(3+)/Fe(2+) transition and intracellular Fe(3+) imaging.
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A monofunctional trinuclear platinum complex with steric hindrance demonstrates strong cytotoxicity against tumor cells.
J. Inorg. Biochem.
PUBLISHED: 03-17-2014
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Polynuclear platinum complexes constitute a special class of hopeful antitumor agents. In this study, a Y-type monofunctional trinuclear platinum complex (MTPC) with 1,3,5-tris(pyridin-2-ylmethoxy)benzene, ammine and chloride as ligands was synthesized and characterized by (1)H NMR and electrospray ionization mass spectrometry (ESI-MS). The DNA binding mode of MTPC was investigated using circular dichroism spectroscopy and gel electrophoresis, and the reactivity of MTPC towards glutathione was studied by (1)H NMR and ESI-MS. The results show that MTPC can affect the conformation of calf-thymus DNA (CT-DNA) significantly and tends to form 1,4-GG rather than 1,2-GG intrastrand crosslinks, which are different from the instance of cisplatin. MTPC reacts with glutathione quite slowly in comparison with cisplatin because of the steric hindrance. The cytotoxicity of MTPC was tested on the human breast cancer cell line MCF-7, the human non-small-cell lung cancer cell line A549, and the human ovarian cancer cell line Skov-3 by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. MTPC is more potent than or comparable to cisplatin. The cellular inhibition mode of MTPC was examined by flow cytometry using MCF-7 cells. MTPC arrests the cell cycle mainly in G2 or M phase, while cisplatin arrests the cell cycle in S phase. Similar to cisplatin, MTPC kills the cells predominantly through an apoptotic pathway.
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Metal-based anticancer chemotherapeutic agents.
Curr Opin Chem Biol
PUBLISHED: 01-08-2014
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Since the discovery of the cisplatin antitumor activity, great efforts have focused on the rational design of metal-based anticancer agents that can be potentially used in cancer chemotherapy. Over the last four decades, a large number of metal complexes have been extensively investigated and evaluated in vitro and in vivo, and some of them were at different stages of clinical studies. Amongst these complexes, platinum (Pt(II) and Pt(IV)), ruthenium (Ru(II) and Ru(III)), gold (Au(I) and Au(III)) and titanium (Ti(IV)) complexes are the most studied metals. We describe here some most recent progresses on Pt(IV) prodrugs which can be activated once enter tumor cells, polynuclear Pt(II) complexes which have unique DNA binding ability and mode, anti-metastatic Ru(II)/Ru(III) complexes, and Au(I)/Au(III) and Ti(IV) antitumor active complexes. The key focuses of these studies lie in finding novel metal complexes which could potentially overcome the hurdles of current clinical drugs including toxicity, resistance and other pharmacological deficiencies.
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In vitro and in vivo imaging application of a 1,8-naphthalimide-derived Zn(2+) fluorescent sensor with nuclear envelope penetrability.
Chem. Commun. (Camb.)
PUBLISHED: 10-31-2013
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A newly developed fluorescent sensor, , shows a specific turn-on response to Zn(2+) and can be excited by visible light. The in situ nuclear Zn(2+) imaging in HeLa and HepG2 cells reveals the nuclear envelope penetrability of the sensor. The specific sensor location in a zebrafish larva was also demonstrated.
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A reversible ratiometric sensor for intracellular Cu2+ imaging: metal coordination-altered FRET in a dual fluorophore hybrid.
Chem. Commun. (Camb.)
PUBLISHED: 07-22-2013
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ICT fluorophore benzoxadiazole with its electron-donating group modified as a Cu(2+) chelator was conjugated with coumarin to construct a new ratiometric sensor with reversible intracellular Cu(2+) imaging ability.
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A red fluorescent turn-on probe for hydrogen sulfide and its application in living cells.
Chem. Commun. (Camb.)
PUBLISHED: 07-18-2013
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A novel selective fluorescent chemosensor has been synthesized with a phenanthrene-fused dipyrromethene structure. Selective binding of Cu(2+) by results in a complex that displays high selectivity and sensitivity for H2S. The signal transduction occurs via reversible formation-separation of the complex and CuS. Its potential utility for biological applications was confirmed by fluorescence imaging of H2S in live cells.
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Thienopyrrole-expanded BODIPY as a potential NIR photosensitizer for photodynamic therapy.
Chem. Commun. (Camb.)
PUBLISHED: 03-27-2013
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The synthesis and characterization of a highly photostable bromo-substituted BODIPY dye (I) fused-ring-expanded with thienopyrrole moieties is reported. The results of MTT assays and flow cytometric analyses in living HeLa cells demonstrate that I has a high singlet oxygen quantum yield (?? = 0.63) and exhibits photocytotoxicity upon irradiation in the NIR region making it potentially suitable for use in PDT.
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Detecting and delivering platinum anticancer drugs using fluorescent maghemite nanoparticles.
Chem. Commun. (Camb.)
PUBLISHED: 02-27-2013
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Rhodamine-embedded maghemite nanoparticles could act as fluorescent drug carriers to track and transport platinum anticancer drugs simultaneously.
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Metal coordination in photoluminescent sensing.
Chem Soc Rev
PUBLISHED: 01-18-2013
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Coordination chemistry plays an essential role in the design of photoluminescent probes for metal ions. Metal coordination to organic dyes induces distinct optical responses which signal the presence of metal species of interest. Luminescent lanthanide (Ln(3+)) and transition metal complexes of d(6), d(8) and d(10) configurations often exhibit unique luminescence properties different from organic dyes, such as high quantum yield, large Stokes shift, long emission wavelength and emission lifetimes, low sensitivity to microenvironments, and can be explored as lumophores to construct probes for metal ions, anions and neutral species. In this review, the design principles and coordination chemistry of metal probes based on mechanisms of PeT, PCT, ESIPT, FRET, and excimer formation will be discussed in detail. Particular attention will be given to rationales for the design of turn-on and ratiometric probes. Moreover, phosphorescent probe design based on Ln(3+) and d(6), d(8) and d(10)-metal complexes are also presented via discussing certain factors affecting the phosphorescence of these metal complexes. A survey of the latest progress in photoluminescent probes for identification of essential metal cations in the human body or toxic metal cations in the environment will be presented focusing on their design rationales and sensing behaviors. Metal complex-based photoluminescent probes for biorelated anions such as PPi, and neutral biomolecules ATP, NO, and H(2)S will be discussed also in the context of their metal coordination-related sensing behaviors and design approaches.
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Improving nuclease activity of copper(II)-terpyridine complex through solubilizing and charge effects of glycine.
J. Inorg. Biochem.
PUBLISHED: 01-09-2013
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Copper complexes are potential metallonucleases that may find application in biotechnology and molecular biology. In this study, a ternary copper-terpyridine complex [Cu(ttpy)(Gly)(NO3)](NO3)·H2O (1) (ttpy=4-p-tolyl-2,2:6,2?-terpyridine) is synthesized and characterized by X-ray crystallography and ESI-MS as an artificial nuclease. Glycine (Gly) is introduced into the complex to enhance the water-solubility and electrostatic affinity for the nucleic acid target. The interaction between complex 1 and DNA has been studied by spectroscopy and gel electrophoresis, using a structural analog [Cu(ttpy)(NO3)2] (2) as the reference. Complex 1 demonstrates an increased DNA binding ability and oxidative cleavage activity towards supercoiled pBR322 DNA as compared with complex 2. The enhanced water-solubility and positive charge of complex 1 may facilitate its access to DNA and formation of hydrogen bonds with the sugar-phosphate backbone. The results indicate that carefully positioned auxiliary groups in a copper complex can significantly affect the substrate binding or activation ability and consequently the nuclease efficiency of the complex.
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Association of 8q24 rs13281615A > G polymorphism with breast cancer risk: evidence from 40,762 cases and 50,380 controls.
Mol. Biol. Rep.
PUBLISHED: 01-05-2013
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The association between a single nucleotide polymorphism rs13281615A > G located in the 8q24 and breast cancer risk is still controversial and ambiguous. Hence, we performed a more convincing and precise estimation of the relationship between 8q24 and breast cancer by meta-analyzing the currently available evidence from literature. PubMed, Ovid, Medline, and Web of Science databases were searched. A total of 10 publications containing 11 studies including 40,762 cases and 50,380 controls were identified. Crude odds ratio with 95 % confidence interval was used to assess the strength of association. We observed that the 8q24 rs13281615A > G polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta analysis. In the stratified analysis by ethnicity, significantly increased risks were also found among Caucasians for all genetic models. For mixed ethnicities, significantly increased risks were found for all genetic models except for the allele contrast model. However, no significantly increased risk was found among Africans for all genetic models. Interestingly, when stratified by BRCA1 mutation carriers status, significantly decreased breast cancer risk was found for allele contrast model. But significantly increased breast cancer risk was found in the BRCA2 mutation carriers for all genetic models except for the recessive model. There was no evidence for significant association between 8q24 rs13281615A > G polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparable models. In conclusion, this meta-analysis suggests that the 8q24 rs13281615A > G polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.
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Unique DNA binding mode of antitumor trinuclear tridentate platinum(II) compound.
Mol. Pharm.
PUBLISHED: 11-16-2011
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The new trinuclear tridentate Pt(II) complex [Pt(3)Cl(3)(hptab)](3+) (1; hptab = N,N,N,N,N,N-hexakis(2-pyridylmethyl)-1,3,5-tris(aminomethyl)benzene) exhibits promising cytotoxic effects in human and mouse tumor cells including those resistant to conventional cisplatin (Dalton Trans. 2006, 2617; Chem. Eur. J. 2009, 15, 5245). The present study is focused on the molecular pharmacology of 1, in particular on its interactions with DNA (which is the major pharmacological target of platinum antitumor drugs), to elucidate more deeply the mechanism underlying its antitumor effects. Results obtained with the aid of methods of molecular biophysics and pharmacology reveal new details of DNA modifications by 1. Complex 1 binds to DNA forming in the absence of proteins and molecular crowding agents mainly trifunctional intrastrand cross-links. In these DNA adducts all three Pt(II) centers of 1 are coordinated to DNA base residues, which leads to extensive conformational alterations in DNA. An intriguing aspect of the DNA-binding mode of this trinuclear Pt(II) complex 1 is that it can cross-link proteins to DNA. Even more interestingly, 1 can cross-link in the presence of molecular crowding agent, which mimics environmental conditions in cell nucleus, two DNA duplexes in a high yield--a feature observed for the first time for antitumor trinuclear platinum complexes. Thus, the concept for the design of agents capable of forming intramolecular tridentate DNA adducts, DNA-protein and interduplex DNA-DNA cross-links based on trinuclear tridentate Pt(II) complexes with semirigid aromatic linkers may result in new compounds which exhibit a variety of biological effects and can be also useful in nucleic acids research.
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Noncovalent interactions between a trinuclear monofunctional platinum complex and human serum albumin.
Inorg Chem
PUBLISHED: 11-11-2011
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Interactions between platinum complexes and human serum albumin (HSA) play crucial roles in the metabolism, distribution, and efficacy of platinum-based anticancer drugs. Polynuclear monofunctional platinum(II) complexes represent a new class of anticancer agents that display distinct molecular characters of pharmacological action from those of cisplatin. In this study, the interaction between a trinuclear monofunctional platinum(II) complex, [Pt(3)LCl(3)](ClO(4))(3) (L = N,N,N,N,N",N"-hexakis(2-pyridylmethyl)-1,3,5-tris(aminomethyl)benzene) (1), and HSA was investigated using ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, circular dichroism spectroscopy, fluorescence spectroscopy, molecular docking, and inductively coupled plasma mass spectrometry. The spectroscopic and thermodynamic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being 14.6 kJ mol(-1) and 145.5 J mol(-1) K(-1), respectively. The reactive sites of HSA to complex 1 mainly locate within its hydrophobic cavity in domain II. Noncovalent actions such as ?-? stacking and hydrophobic bonding are the primary contributors to the interaction between HSA and complex 1, which is different from the scenario for cisplatin in similar conditions. The results suggest that the connection between complex 1 and HSA is reversible, and therefore the cytotoxic activity of the complex could be preserved during blood circulation.
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In vitro and in vivo fluorescent imaging of a monofunctional chelated platinum complex excitable using visible light.
Inorg Chem
PUBLISHED: 10-28-2011
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The biological fluorescent distribution of a model antitumor monofunctional platinum(II) complex bearing a 7-nitro-2,1,3-benzoxadiazole fluorophore can be visualized in breast carcinoma MCF-7 cells, pulmonary carcinoma A549 cells, kidney epithelial 293T cells, and zebrafish larva.
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Three-dimensional photoacoustic tomography based on the focal-line concept.
J Biomed Opt
PUBLISHED: 09-29-2011
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A full ring ultrasonic array-based photoacoustic tomography system was recently developed for small animal brain imaging. The 512-element array is cylindrically focused in the elevational direction, and can acquire a two-dimensional (2D) image in 1.6 s. In this letter, we demonstrate the three-dimensional (3D) imaging capability of this system. A novel 3D reconstruction algorithm was developed based on the focal-line concept. Compared to 3D images acquired simply by stacking a series of 2D images, the 3D focal-line reconstruction method renders images with much less artifacts, and improves the elevational resolution by 30% and the signal-to-noise ratio by two times. The effectiveness of the proposed algorithm was first validated by numerical simulations and then demonstrated with a hair phantom experiment and an ex vivo mouse embryo experiment.
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Photoacoustic tomography of monkey brain using virtual point ultrasonic transducers.
J Biomed Opt
PUBLISHED: 08-03-2011
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A photoacoustic tomography system (PAT) using virtual point ultrasonic transducers was developed and applied to image a monkey brain. The custom-built transducers provide a 10-fold greater field-of-view (FOV) than finite-aperture unfocused transducers as well as an improved signal-to-noise ratio (SNR) and reduced artifacts rather than negative-lens transducers. Their tangential resolution, radial resolution, and (SNR) improvements were quantified using tissue phantoms. Our PAT system can achieve high uniformity in both resolution (<1 mm) and SNR (>8) within a large FOV of 6 cm in diameter, even when the imaging objects are enclosed by a monkey skull. The cerebral cortex of a monkey brain was accurately mapped transcranially, through a skull ranging from 2 to 4 mm in thickness. This study demonstrates that PAT can overcome the optical and ultrasound attenuation of a relatively thick skull and can potentially be applied to human neonatal brain imaging.
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Cellular and biomolecular responses of human ovarian cancer cells to cytostatic dinuclear platinum(II) complexes.
Apoptosis
PUBLISHED: 08-02-2011
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Polynuclear platinum(II) complexes represent a class of potential anticancer agents that have shown promising pharmacological properties in preclinical studies. The nature of cellular responses induced by these complexes, however, is poorly understood. In this research, the cellular responses of human ovarian cancer COC1 cells to dinuclear platinum(II) complexes {[cis-Pt(NH?)?Cl]?L¹}(NO?)? (1) and {[cis-Pt(NH?)?Cl]?L²}(NO?)? (2) (L¹ = ?,?-diamino-p-xylene, L² = 4,4-methylenedianiline) has been studied using cisplatin as a reference. The effect of platinum complexes on the proliferation, death mode, mitochondrial membrane potential, and cell cycle progression has been examined by MTT assay and flow cytometry. The activation of cell cycle checkpoint kinases (CHK1/2), extracellular signal-regulated kinases (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) of the cells by the complexes has also been analyzed using phospho-specific flow cytometry. Complex 1 is more cytotoxic than complex 2 and cisplatin at most concentrations; complex 2 and cisplatin are comparably cytotoxic. These complexes kill the cells through an apoptotic or apoptosis-like pathway characterized by exposure of phosphatidylserine and dissipation of mitochondrial membrane potential. Complex 1 shows the strongest inductive effect on the morphological changes of the cells, followed by cisplatin and complex 2. Complexes 1 and 2 arrest the cell cycle in G2 or M phase, while cisplatin arrests the cell cycle in S phase. The influence of these complexes on CHK1/2, ERK1/2, and p38 MAPK varies with the dose of the drugs or reaction time. Activation of phospho-ERK1/2 and phospho-p38 MAPK by these complexes is closely related to the cytostatic activity. The results demonstrate that dinuclear platinum(II) complexes can induce some cellular responses different from those caused by cisplatin.
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Cytotoxic palladium(II) complexes of 8-aminoquinoline derivatives and the interaction with human serum albumin.
J. Inorg. Biochem.
PUBLISHED: 07-30-2011
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Palladium(II) complexes are potential antitumor metallodrugs for their chemical resemblance to platinum(II) complexes. Two palladium(II) complexes (1 and 2) in the formula of [PdL(n)Cl] [L(1) = N-(tert-butoxycarbonyl)-l-methionine-N-8-quinolylamide, L(2) = L-alanine-N-8-quinolylamide] have been synthesized accordingly. The structures of the complexes were fully characterized by X-ray crystallography. The palladium(II) center in 1 is coordinated by two N atoms and an S atom from L(1) with one chloride anion as the leaving group; while that in 2 is coordinated by three N atoms from L(2) with one chloride anion as the leaving group. The interaction between complex 1 and human serum albumin (HSA) has been investigated using fluorescence and circular dichroism spectroscopies. The complex seems to react with HSA chiefly through hydrophobic and electrostatic interactions, and it does not alter the ?-helical nature of HSA. The cytotoxicity of these complexes has been tested against the human cervical cancer (HeLa), human mammary cancer (MCF-7), and human lung cancer (A-549) cell lines. Complex 1 displays a cytotoxic activity comparable to that of cisplatin, but complex 2 is less active than cisplatin.
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Terbium(III) complex as a luminescent sensor for human serum albumin in aqueous solution.
Chem. Commun. (Camb.)
PUBLISHED: 06-20-2011
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A terbium(III) complex gives off strong luminescence upon reacting with human serum albumin in aqueous solution, which can be used to detect the presence and structural modifications of this protein.
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Monofunctional platinum complexes containing a 4-nitrobenzo-2-oxa-1,3-diazole fluorophore: distribution in tumour cells.
Dalton Trans
PUBLISHED: 06-17-2011
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Two monofunctional platinum(II) complexes, cis-[PtL(NH(3))(2)Cl]NO(3) (1) and cis-[PtL(NH(3))(2)Cl]NO(3) (2) {L = N-methyl-7-nitro-N-(2-(pyridin-2-yl)ethyl)benzo[c][1,2,5]-oxadiazol-4-amine, L = 7-nitro-N-(2-(pyridin-2-yl)ethyl)benzo[c][1,2,5] oxadiazol-4-amine}, have been synthesized and characterized. The X-ray single crystal structure of complex 1 shows that platinum(II) is coordinated in a square-planar geometry with a [PtN(3)Cl] setting. Fluorescence profiles of the complexes show that complex 1 is more suitable for cellular imaging than complex 2. The cellular uptake and distribution of complex 1 in the human cervical cancer HeLa cells were studied using confocal microscopy. Complex 1 enters the cells slowly, induces cytoplasmic vacuolations, and accumulates in the nucleoli. These results suggest that monofunctional platinum(II) complexes can stimulate tumour cells to undergo a nonapoptotic death process, which is distinct from the apoptosis induced by cisplatin.
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Attenuation of antigen-induced airway hyperresponsiveness and inflammation in CXCR3 knockout mice.
Respir. Res.
PUBLISHED: 05-04-2011
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CD8+ T cells participate in airway hyperresponsiveness (AHR) and allergic pulmonary inflammation that are characteristics of asthma. CXCL10 by binding to CXCR3 expressed preferentially on activated CD8+ T cells, attracts T cells homing to the lung. We studied the contribution and limitation of CXCR3 to AHR and airway inflammation induced by ovalbumin (OVA) using CXCR3 knockout (KO) mice.
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Six new metal-organic frameworks based on polycarboxylate acids and V-shaped imidazole-based synthon: syntheses, crystal structures, and properties.
Inorg Chem
PUBLISHED: 02-08-2011
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Solvothermal reactions of 4,4-bis(imidazol-1-yl)diphenyl ether (BIDPE) with deprotonated 5-hydroxy-isophthalic acid (5-OH-H(2)bdc), and benzene-1,3,5-tricarboxylic acid (H(3)btc) in the presence of cadmium(II), zinc(II), cobalt(II), nickel(II), and manganese(II) salts in H(2)O or H(2)O/DMF produced six new complexes, namely, [Cd(BIDPE)(5-OH-bdc)·H(2)O](n) (1), [Co(BIDPE)(5-OH-bdc)·H(2)O](n) (2), [Zn(3)(BIDPE)(3)(5-OH-bdc)(3)·4H(2)O](n) (3), [Ni(BIDPE)(2)(5-OH-bdc)(H(2)O)·3H(2)O](n) (4), {[Mn(2)(BIDPE)(2)(5-OH-bdc)(2)](n) (5), and [Ni(BIDPE)(2)(Hbtc)(H(2)O)](n) (6). These complexes were characterized by elemental analysis, IR spectroscopy, and X-ray single-crystal diffraction. Compounds 1 and 2 reveal the same two-dimensional (2D) sheets with a 32-membered [(Cd/Co)(2)(BIDPE)(2)] metallocyclic ring constructed from BIDPE and 5-OH-H(2)bdc with Cd or Co salts. For compound 3, six identical 2D sheets are polycatenated in parallel to form a rare 2D ? 2D framework; it displays ferroelectric behavior with a remnant electric polarization (P(r)) of 0.033 ?C/cm(2) and an electric coercive field (E(c)) of 11.15 kV/cm. In compounds 4 and 6, only one carboxyl group coordinated to the Ni atom from 5-OH-H(2)bdc or H(3)btc. Compound 5 exists as binuclear Mn clusters, which are linked by BIDPE and 5-OH-H(2)bdc to generate a 2D sheet and displays weak antiferromagnetic character. In addition, the thermal stabilities and photochemical properties of these new complexes have been studied.
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A novel terpyridine/benzofurazan hybrid fluorophore: metal sensing behavior and application.
Dalton Trans
PUBLISHED: 11-18-2010
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Terpyridine/benzofurazan conjugation results in a new hybrid fluorophore of the colorimetric sensing ability for Fe(2+) and fluorimetric sensing ability for XII group cations. The improved emission properties and cell imaging ability imply it is a suitable platform to construct a fluorescent sensor for metal imaging in biological systems.
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Reversible DNA condensation induced by a tetranuclear nickel(II) complex.
Chemistry
PUBLISHED: 10-23-2010
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DNA condensing agents play a critical role in gene therapy. A tetranuclear nickel(II) complex, [Ni(II)(4)(L-2H)(H(2)O)(6)(CH(3)CH(2)OH)(2)]·6NO(3) (L=3,3,5,5-tetrakis{[(2-hydroxyethyl)(pyridin-2-ylmethyl)amino]methyl}biphenyl-4,4-diol), has been synthesized as a nonviral vector to induce DNA condensation. X-ray crystallographic data indicate that the complex crystallizes in the monoclinic system with space group P2(1)/n, a=10.291(9), b=24.15(2), c=13.896(11) Å, and ?=98.175(13)°. The DNA condensation induced by the complex has been investigated by means of UV/Vis spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, dynamic light scattering, atomic force microscopy, gel electrophoresis assay, and zeta potential analysis. The complex interacts strongly with DNA through electrostatic attraction and induces its condensation into globular nanoparticles at low concentration. The release of DNA from its compact state has been achieved using the chelator ethylenediaminetetraacetic acid (EDTA) for the first time. Other essential properties, such as DNA cleavage inactivity and biocompatibility, have also been examined in vitro. In general, the complex satisfies the requirements of a gene vector in all of these respects.
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His-oriented peptide hydrolysis promoted by cis-[Pt(en)(H2O)2]2+: a new specific peptide cleavage site.
Inorg Chem
PUBLISHED: 08-04-2010
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The new specific hydrolysis of histidine-containing peptides promoted by cis-[Pt(en)(H(2)O)(2)](2+) was investigated by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance spectrometry (NMR). MS determination demonstrated that cis-[Pt(en)(H(2)O)(2)](2+) anchors to AcGHG with the stoichiometry of either 1:1 or 2:1 (Pt/peptide), but only with 1:1 stoichoimetry to AcGHL. Cis-[Pt(en)(H(2)O)(2)](2+) is able to promote the cleavage of the first downstream peptide bond from histidine at 60 degrees C and pH 2.65, and Pt-anchored peptides are the essential intermediates for the promoted hydrolysis. Moreover, the larger amount of Pt(II) complex results in higher fragmental yield and higher hydrolysis rate. In the presence of 1 equiv of Pt(II) complex, (1)H NMR determination confirmed the apparent first-order kinetics of the Pt(II)-promoted hydrolysis and the hydrolysis rate for AcGHG and AcGHL is 0.20 day(-1) and 0.14 day(-1), respectively. Moreover, Pt(II) coordinating to histidine imidazole is the key step to form the Pt(II)-anchored peptides. The Pt(II)-activating the first His-downstream carbonyl group via synergic coordinating to His imidazole and carbonyl O atom has been proposed for the Pt(II)-promoted his-oriented peptide hydrolysis. The lower rate for AcGHL should be correlated to the steric hindrance of Leu side chain to the second Pt(II) coordinating to tripeptide. In addition, the newly confirmed specific His-oriented peptide cleavage site implies a new potential strategy for target cleavage of peptides or proteins.
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Solvothermal syntheses, structures, and physical properties of four new coordination compounds constructed from a bent dicarboxylate ligand.
Dalton Trans
PUBLISHED: 08-03-2010
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Four new coordination compounds, namely {[Cd(3)(L)(2)(mu(3)-OH)(2)(H(2)O)] x H(2)O}(n) (1), {Ni(L)(bipy)}(n) (2), {Cu(3)(L)(2)(bipy)(mu(2)-OH)(2)(DMF)(2)}(n) (3), and {Co(2)L(2)(H(2)L)(H(2)O)}(n) (4), have been synthesized by the solvothermal reaction of 4,4-(hexafluoroisopropylidene)bis(benzoic acid) (H(2)L) with different transition metal ions in the presence of co-ligand 4,4-bipyridine (bipy). Compound 1 displays a three-dimensional (3D) framework containing infinite bands constructed of heptanuclear cadmium clusters. In compound 2, [Ni(2)C(2)O(4)] secondary building units (SBUs) are linked by L(2-) ligands into a 1D ribbon, which are further assembled into a two-dimensional (2D) non-interpenetrated structure with {4(4) x 6(2)} topology. Compound 3 possesses a 3D framework with a new topology of {4(3)}(2){4(6) x 6(14) x 8(8)} net, while the structure of 4 is a duplicate interpenetrated 3D framework with {4(12) x 6(3)} net. Temperature-dependent magnetic studies reveal that 3 exhibits ferromagnetic coupling between adjacent Cu(II) ions. The photoluminescent property of 1 has been studied in the solid state at room temperature.
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A highly sensitive ratiometric fluorescent probe for Cd2+ detection in aqueous solution and living cells.
Chem. Commun. (Camb.)
PUBLISHED: 07-28-2010
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A ratiometric fluorescent Cd(2+) sensor DBITA which featured the Cd(2+)-induced red-shift of emission (53 nm) and picomolar sensitivity in both aqueous media and living cells was developed.
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Sentinel lymph nodes in the rat: noninvasive photoacoustic and US imaging with a clinical US system.
Radiology
PUBLISHED: 06-25-2010
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To evaluate in vivo sentinel lymph node (SLN) mapping by using photoacoustic and ultrasonographic (US) imaging with a modified clinical US imaging system.
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Calibration-free absolute quantification of optical absorption coefficients using acoustic spectra in 3D photoacoustic microscopy of biological tissue.
Opt Lett
PUBLISHED: 06-16-2010
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Optical absorption is closely associated with many physiological important parameters, such as the concentration and oxygen saturation of hemoglobin, and it can be used to quantify the concentrations of nonfluorescent molecules. We propose a method to use acoustic spectra of photoacoustic signals to quantify the absolute optical absorption. This method is self-calibrating and thus insensitive to variations in the optical fluence. Factors such as system bandwidth and acoustic attenuation can affect the quantification but can be canceled by dividing the acoustic spectra measured at two optical wavelengths. Using optical-resolution photoacoustic microscopy, we quantified the absolute optical absorption of black ink samples with various concentrations. We also quantified both the concentration and oxygen saturation of hemoglobin in a live mouse in absolute units.
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Compressed sensing in photoacoustic tomography in vivo.
J Biomed Opt
PUBLISHED: 05-13-2010
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The data acquisition speed in photoacoustic computed tomography (PACT) is limited by the laser repetition rate and the number of parallel ultrasound detecting channels. Reconstructing an image with fewer measurements can effectively accelerate the data acquisition and reduce the system cost. We adapt compressed sensing (CS) for the reconstruction in PACT. CS-based PACT is implemented as a nonlinear conjugate gradient descent algorithm and tested with both phantom and in vivo experiments.
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A prostacyclin analogue, iloprost, protects from bleomycin-induced pulmonary fibrosis in mice.
Respir. Res.
PUBLISHED: 03-20-2010
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Metabolites of arachidonic acid such as prostacyclin (PGI2) have been shown to participate in the pathogenesis of pulmonary fibrosis by inhibiting the expression of pro-inflammatory and pro-fibrotic mediators. In this investigation, we examined whether iloprost, a stable PGI2 analogue, could prevent bleomycin-induced pulmonary inflammation and fibrosis in a mouse model.
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Mechanistic insights into antitumor effects of new dinuclear cis Pt(II) complexes containing aromatic linkers.
Biochem. Pharmacol.
PUBLISHED: 03-06-2010
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The primary objective was to understand more deeply the molecular mechanism underlying different antitumor effects of dinuclear Pt(II) complexes containing aromatic linkers of different length, {[cis-Pt(NH(3))(2)Cl](2)(4,4-methylenedianiline)}(2+) (1) and {[cis-Pt(NH(3))(2)Cl](2)(alpha,alpha-diamino-p-xylene)}(2+) (2). These complexes belong to a new generation of promising polynuclear platinum drugs resistant to decomposition by sulfur nucleophiles which hampers clinical use of bifunctional polynuclear trans Pt(II) complexes hitherto tested. Results obtained with the aid of methods of molecular biophysics and pharmacology reveal differences and new details of DNA modifications by 1 and 2 and recognition of these modifications by cellular components. The results indicate that the unique properties of DNA interstrand cross-links of this class of polynuclear platinum complexes and recognition of these cross-links may play a prevalent role in antitumor effects of these metallodrugs. Moreover, the results show for the first time a strong specific recognition and binding of high-mobility-group-domain proteins, which are known to modulate antitumor effects of clinically used platinum drugs, to DNA modified by a polynuclear platinum complex.
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Fast cleavage of a diselenide induced by a platinum(II)-methionine complex and its biological implications.
J. Inorg. Biochem.
PUBLISHED: 02-06-2010
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Platinum-based anticancer drugs such as cisplatin induce increased oxidative stress and oxidative damage of DNA and other cellular components, while selenium plays an important role in the antioxidant defense system. In this study, the interaction between a platinum(II) methionine (Met) complex [Pt(Met)Cl(2)] and a diselenide compound selenocystine [(Sec)(2)] was studied by electrospray ionization mass spectrometry, high performance liquid chromatography mass spectrometry, and (1)H NMR spectroscopy. The results demonstrate that the diselenide bond in (Sec)(2) can readily and quickly be cleaved by the platinum complex. Formation of the selenocysteine (Sec) bridged dinuclear complex [Pt(2)(Met-S,N)(2)(?-Sec-Se,Cl)](3+) and Sec chelated species [Pt(Met-S,N)(Sec-Se,N)](2+) was identified at neutral and acidic media, which seems to result from the intermediate [Pt(Met-S,N)(Sec-Se)Cl](+). An accelerated formation of S-Se and S-S bonds was also observed when (Sec)(2) reacted with excessive glutathione in the presence of [Pt(Met)Cl(2)]. These results imply that the mechanism of activity and toxicity of platinum drugs may be related to their fast reaction with seleno-containing biomolecules, and the chemoprotective property of selenium agents against cisplatin-induced toxicity could also be connected with such reactions.
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Promotive effect of the platinum moiety on the DNA cleavage activity of copper-based artificial nucleases.
Inorg Chem
PUBLISHED: 02-04-2010
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Copper-based artificial metallonucleases are likely to satisfy more biomedical requirements if their DNA cleavage efficiency and selectivity could be further improved. In this study, two copper(II) complexes, [CuL(1)Cl(2)] (1) and [CuL(2)Cl(2)] (2), and two copper(II)-platinum(II) heteronuclear complexes, [CuPtL(1)(DMSO)Cl(4)] (3) and [CuPtL(2)(DMSO)Cl(4)] (4), were synthesized using two bifunctional ligands, N-[4-(2-pyridylmethoxy)benzyl]-N,N-bis(2-pyridylmethyl)amine (L(1)) and N-[3-(2-pyridylmethoxy)benzyl]-N,N-bis(2-pyridylmethyl)amine (L(2)). These complexes have been characterized by elemental analysis, electrospray ionization mass spectrometry, IR spectroscopy, and UV-vis spectroscopy. The DNA binding ability of these complexes follows an order of 1 < 2 < 3 < 4, as revealed by the results of spectroscopy and agarose gel electrophoresis studies. Their cleavage activity toward supercoiled pUC19 plasmid DNA is prominent at micromolar concentration levels in the presence of ascorbic acid. The introduction of a platinum(II) center to the copper(II) complexes induces a significant enhancement in cleavage activity as compared with copper(II) complexes alone. These results show that the presence of a platinum(II) center in copper(II) complexes strengthens both their DNA binding ability and DNA cleavage efficiency.
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Platinum(II) compounds bearing bone-targeting group: synthesis, crystal structure and antitumor activity.
Chem. Commun. (Camb.)
PUBLISHED: 01-16-2010
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Platinum(II) complexes bearing geminal bisphosphonate moieties have excellent solubility in both organic and aqueous solutions and show considerable cytotoxicity against human osteosarcoma (MG-63) and ovarian cancer (COC1) cell lines with different apoptotic pathways from that of cisplatin.
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The role of bridging ligands in determining DNA-binding ability and cross-linking patterns of dinuclear platinum(II) antitumour complexes.
Dalton Trans
PUBLISHED: 11-13-2009
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The DNA binding ability and binding mode of platinum complexes are crucial factors that govern their cytotoxic activity. In this work, circular dichroism spectroscopy, gel electrophoresis and MALDI-TOF MS spectrometry combined with enzymatic degradation have been used to elucidate the role of bridging ligands in DNA-binding ability and cross-linking patterns of two dinuclear antitumour active platinum(II) complexes, {[cis-Pt(NH(3))(2)Cl](2)L1}(NO(3))(2) (1, L1= 4,4-methylenedianiline) and {[cis-Pt(NH(3))(2)Cl](2)L2}(NO(3))(2) (2, L2 = alpha,alpha-diamino-p-xylene). Although both complexes have two cis-diammine-Pt(II) moieties (1,1/c,c), complex 1 exhibits much higher DNA-binding ability than complex 2. The former readily forms both 1,3- and 1,4-intrastrand cross-links with DNA oligonucleotides, while the latter preferentially forms 1,4- rather than 1,3-intrastrand cross-links. Cytotoxicity studies against a human non-small-cell lung cancer cell line (A549) demonstrate that complex 1 has higher activity than 2. These results show that the linker properties play a critical role in controlling the DNA-binding and cross-linking abilities and in modulating the cytotoxicity of dinuclear platinum complexes.
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On the speckle-free nature of photoacoustic tomography.
Med Phys
PUBLISHED: 10-09-2009
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A long-standing conundrum is why photoacoustic tomography (PAT) possesses the unique ability to produce images devoid of speckle artifacts while all other coherent imaging technologies do not.
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A visible light excitable fluorescent sensor for triphosphate/pyrophosphate based on a diZn2+ complex bearing an intramolecular charge transfer fluorophore.
Dalton Trans
PUBLISHED: 08-24-2009
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Triphosphate or pyrophosphate can be recognised by a diZn(2+) complex of bis(BPEA)-appended intramolecular charge transfer fluorophore 4-amino-7-aminosulfonyl-2,1,3-benzoxadiazole, displaying a 5-6 fold fluorescent enhancement at 576 nm.
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DNA binding property, nuclease activity and cytotoxicity of Zn(II) complexes of terpyridine derivatives.
Biometals
PUBLISHED: 08-14-2009
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Two zinc(II) terpyridine complexes Zn(atpy)(2)(PF(6))(2) (1) (atpy = 4-p-N9-adeninylmethylphenyl-2,2:6,2-terpyridine) and Zn(ttpy)(2)(PF(6))(2) (2) (ttpy = 4-p-tolyl-2,2:6,2-terpyridine) have been synthesized and characterized by elemental analysis, (1)H NMR and electrospray mass spectroscopy. The structure of complex 2 was also determined by X-ray crystallography, which revealed a ZnN(6) coordination in an octahedral geometry with two terpyridine acting as equatorial ligands. The circular dichroism data showed that complex 1 exhibited an ICD signal at around 300 nm and induced more evident disturbances on DNA base stacking than complex 2, reflecting the impact of the adenine moiety on DNA binding modes. Complex 1 exhibited higher cleavage activity to supercoiled pUC 19 DNA than complex 2 under aerobic conditions, suggesting a promotional effect of adenine moiety in DNA nuclease ability. Interestingly, both complexes demonstrated potent in vitro cytotoxicity against a series human tumor cell lines such as human cervix carcinoma cell line (HeLa), human liver carcinoma cell line (HepG2), human galactophore carcinoma cell line (MCF-7) and human prostate carcinoma cell line (pc-3). The cytotoxicity is averagely 10 times more active than the anticancer drug cisplatin.
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Systematic characterization on electronic structures and spectra for a series of complexes, M(IDB)Cl2 (M = Mn, Fe, Co, Ni, Cu and Zn): a theoretical study.
J Mol Model
PUBLISHED: 06-23-2009
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Theoretical studies on the coordination stabilities, spectra and DNA-binding trend for the series of metal-varied complexes, M(IDB)Cl2 (M = Mn, Fe, Co, Ni, Cu and Zn; IDB = N, N-bis(2-benzimidazolylmethyl) amine), have been carried out by using the DFT/B3LYP method and PCM model. The calculated coordination stabilities (S) for these complexes present a trend of S(Ni) > S(Co) > S(Fe) > S(Cu) > S(Zn) > S(Mn). It has been estimated from the molecular orbital energies of the complexes that the DNA-binding affinities (A) of the complexes are in the order of A(Zn) < A(Mn) < A(Fe) approximately A(Co) < A(Ni) < A(Cu). The studied results indicate that the Cu, Ni and Co complexes with large coordination stabilities present the low virtual orbitals, consequently yielding to the favorable DNA-binding affinities. The spectral properties of excitation energies and oscillator strengths for M(IDB)Cl2 in the ultraviolet region were calculated by TD-DFT/B3LYP method.
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Three new heterothiometallic cluster polymers with fascinating topologies.
Inorg Chem
PUBLISHED: 06-09-2009
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Three new heterothiometallic cluster polymers with fascinating topologies have been synthesized by the self-assembly of preformed heterothiometallic cluster monomers and appropriate ligands. Reaction of the monomeric cubic-shaped cluster [Et(4)N](3)[MoOS(3)Cu(3)I(4)] with the D(2h) symmetry rigid bidentate 4,4-bipy (4,4-bipyridine) gave a two-dimensional (2D) layer compound [Mo(2)O(2)S(6)Cu(6)I(2)(4,4-bipy)(3)(H(2)O)](n) (1); the assembly of pentanuclear cluster monomer [Et(4)N](4)[WS(4)Cu(4)I(6)] with C(s)-symmetrical bpe (1,2-bis(4-pyridyl)ethane) afforded a 2D layer compound [WS(4)Cu(4)I(2)(bpe)(3)(H(2)O)](n) (2), and the assembly of heptanuclear cluster monomer [Et(4)N](4)[WS(4)Cu(6)I(8)] with D(3h) symmetry trigonal planar ligand timtz (2, 4, 6-tri(1H-imidazol-1-yl)-1, 3, 5-triazine) afforded a three-dimensional (3D) compound [WS(4)Cu(6)I(4)(timtz)(8/3)(H(2)O)(12)](n) (3). X-ray crystallographic analysis reveals that 1 crystallizes in trigonal space group R3c with 2D 3(6)-hxl net which is the first heterothiometallic superamolecular structure based on a twin cubic-shaped cluster monomer and also the first example of 4,4-bipy-connected compound of this net. 2 crystallizes in tetragonal space group P4(2) with distorted 2D 3(6)-hxl net which is the first flexible-ligand-based compound of this topology; while 3 has a 3D net with the high symmetry of cubic space group I43d, and has a novel alpha-C(3)N(4) topology, which is the maximum symmetry for this net topology. The gas sorption isotherm was measured for 3 to exhibit type-III sorption behavior.
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Effects of cyclen and cyclam on zinc(II)- and copper(II)-induced amyloid beta-peptide aggregation and neurotoxicity.
Inorg Chem
PUBLISHED: 06-06-2009
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The aggregation of amyloid beta-peptide (Abeta) in plaques in brain tissue is highly associated with Alzheimers disease (AD). Aberrant homeostasis of cerebral metals such as Zn(2+) and Cu(2+) may facilitate the formation of the pathogenetic amyloid plaques. Further, the accumulation of redox-active Cu(2+) in these plaques leads to the generation of reactive oxygen species, which mediates the conspicuous oxidative damage to the brain in AD. In this study, the effect of macrocyclic polyamine chelators, cyclen and cyclam, on the aggregation of Abeta40 induced by Zn(2+) or Cu(2+) was investigated using turbidometry, thioflavin T fluorescence spectroscopy, electrospray ionization mass spectrometry, inductively coupled plasma mass spectrometry, BCA protein assay, circular dichroism spectroscopy, and atomic force microscopy. The solubility of Zn(2+)- or Cu(2+)-induced Abeta40 aggregates is greatly increased by cyclen or cyclam as compared to that without chelators, and the solubilization is not affected by other essential metal ions such as Ca(2+) and Mg(2+). Moreover, the metal-induced beta-sheet structure of Abeta40 can be reconverted to its original random coil conformation, and the generation of H(2)O(2) mediated by the Cu-Abeta40 complex can also be inhibited by these chelators. Preliminary tests on neuronal cells indicate that these chelators are capable of reducing the toxicity of metal-Abeta40 aggregates. These observations suggest that cyclen and cyclam could be lead compounds as neuroprotective or neurorescue agents for the treatment of AD.
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TNRC9/LOC643714 polymorphisms are not associated with breast cancer risk in Chinese women.
Eur. J. Cancer Prev.
PUBLISHED: 04-29-2009
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Variants in several genes are known to confer increased susceptibility to breast cancer, but the frequencies of these mutations in the population are very rare and different between race or ethnic groups. Genetic variation in trinucleotide repeat containing 9 (TNRC9) and the hypothetical gene LOC643714 (TNRC9/LOC643714) is a newly described risk factor for breast cancer. Here, we investigated the association among the three single nucleotide polymorphisms (SNPs) in TNRC9/LOC643714 and breast cancer risk and clinico-pathological parameters in a hospital-based Chinese population. Genomic DNA was extracted from peripheral blood lymphocytes. Polymerase chain reaction-ligation detection reaction was used to genotype 321 breast cancer cases and 330 controls. In addition, the representative polymerase chain reaction products were subjected to direct DNA sequencing to confirm the accuracy of this method. The odds ratios and 95% confidence intervals were calculated by an unconditional logistic regression model. There was no significant association between the risk of breast cancer and three SNPs of TNRC9/LOC643714 gene polymorphisms and their haplotypes. No significant correlation was found between the TNRC9/LOC643714 polymorphisms and age at diagnosis, lymph node metastases, estrogen receptor status, or progesterone receptor status, respectively. None of these three SNPs of TNRC9/LOC643714 gene is associated with individual susceptibility to breast cancer in Chinese women.
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Reactivity of platinum-based antitumor drugs towards a Met- and His-rich 20mer peptide corresponding to the N-terminal domain of human copper transporter 1.
J. Biol. Inorg. Chem.
PUBLISHED: 04-08-2009
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Cellular uptake of platinum-based antitumor drugs is a critical step in the mechanism of the drug action and associated resistance, and deeper understanding of this step may inspire development of novel methods for new drugs with reduced resistance. Human copper transporter 1 (hCtr1), a copper influx protein, was recently found to facilitate the cellular entry of several platinum drugs. In the work reported here, we constructed a Met- and His-rich 20mer peptide (hCtr1-N20) corresponding to the N-terminal domain of hCtr1, which is the essential domain of hCtr1 for transporting platinum drugs. The interactions of the peptide with cisplatin and its analogues, including transplatin, carboplatin, oxaliplatin, and [Pt(L: -Met)Cl(2)], were explored at the molecular level. Electrospray ionization (ESI) mass spectrometry (MS) data revealed that all of the platinum(II) complexes used in present study can bind to hCtr1-N20 in 1:1 and 2:1 stoichiometry. Four Met residues should be involved in binding to cis-platinum complexes on the basis of the tandem MS spectrometry and previously reported data. Time-dependent 2D [(1)H,(15)N] heteronuclear single quantum coherence NMR spectra indicate the reaction of cisplatin with hCtr1-N20 is a stepwise process. The intermediate, however, is transient, which is consistent with the ESI-MS results. Time-dependent ESI-MS data revealed that the geometry and the properties of both the leaving and the nonleaving groups of platinum(II) complexes play essential roles in controlling the reactivity and formation of the final products with hCtr1-N20.
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DNA cross-linking patterns induced by an antitumor-active trinuclear platinum complex and comparison with its dinuclear analogue.
Chemistry
PUBLISHED: 04-08-2009
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The DNA binding and cross-linking modes of a trinuclear platinum complex [Pt(3)Cl(3)(hptab)][ClO(4)](3) (1; hptab = N,N,N,N,N,N-hexakis(2-pyridylmethyl)-1,3,5-tris(aminomethyl)benzene) and its dinuclear analogue [Pt(2)Cl(2)(m-tpxa)]Cl(2) (2; m-tpxa = N,N,N,N-tetra(2-pyridylmethyl)-m-xylylene diamine) are reported and compared. The adducts of 1 and 2 with 18-mer duplex N1, 5-d(GAAGAAGTCACAAAATGT)-35-d(ACATTTTGTGACTTCTTC)-3, have been characterized by means of denaturing polyacrylamide gels, Maxam-Gilbert sequencing, and MALDI-TOF mass spectrometry combined with enzymatic degradation to obtain insights into structural features responsible for the differences in their antitumor activities. The cytotoxic-active complex 1 readily forms various DNA adducts, such as through 1,3- and 1,4-intrastrand cross-links, and in particular, the unique and unprecedented interstrand cross-linked triadducts. In contrast, the cytotoxic-inactive complex 2 preferentially forms 1,4-intrastrand rather than 1,3-intra- and -interstrand cross-links. Digestion of the DNA adducts of 1 shows that the cleavage is completely blocked at one nucleotide before the cross-linked guanine residues on the opposite strand, a feature that appears to be unprecedented in antitumor platinum complexes. In the case of 2, the cleavage bypasses the first platinated guanine site and stops at one nucleotide prior to the second platinated site, confirming that very few 1,3-intrastrand cross-links are formed by 2. These results are supported by molecular-modeling studies of intra- and interstrand cross-links of duplex N1 with 1 and 2. The remarkable differences between 1 and 2 in DNA binding and cross-linking provide mechanistic insights into their different cytotoxicity against the tumor cell lines; these insights are useful for designing future antitumor agents.
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Characterization and cellular uptake of platinum anticancer drugs encapsulated in apoferritin.
J. Inorg. Biochem.
PUBLISHED: 03-11-2009
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Clinical application of platinum-based anticancer drugs is largely limited by severe general toxicity and drug resistance. Drug delivery systems with tumor-targeting potential are highly desired for improving the efficacy and applicability of these drugs. This study describes an alternative strategy for the delivery of platinum drugs (cisplatin, carboplatin and oxaliplatin) by encapsulating each of them in the cavity of apoferritin (AFt). The encapsulation was achieved through manipulating the pH-dependent unfolding-refolding process of AFt at pH 2.0 and 7.4, respectively, in saturated drug solution. UV-vis spectrometry, circular dichroism spectrometry, dynamic light scattering, and inductively coupled plasma mass spectrometry were used to characterize the AFt-drug complexes. The loading capacity of AFt varies with respective drugs and the structural integrity of the protein shell remains intact after encapsulation. In vitro assays on the rat pheochromocytoma cell line (PC12) show that AFt-cisplatin inhibits the cells in a slow but sustaining mode and the cellular uptake of platinum is enhanced by AFt. AFt-carboplatin and AFt-oxaliplatin complexes only exhibit a marginal cytotoxicity towards this cell line under similar concentrations.
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Preliminary investigation of the clinical significance of detecting circulating tumor cells enriched from lung cancer patients.
J Thorac Oncol
PUBLISHED: 03-06-2009
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Enumeration of circulating tumor cells (CTCs) may be valuable for lung cancer treatment and monitoring cancer patient relapse. In the present study we report clinical significance of lung cancer CTC.
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A Zn2+ fluorescent sensor derived from 2-(pyridin-2-yl)benzoimidazole with ratiometric sensing potential.
Org. Lett.
PUBLISHED: 02-10-2009
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A fluorescent Zn(2+) sensor based on the 2-(2-pyridinyl)benzoimidazole (2-PBI) fluorophore has been devised by incorporation with a Zn(2+) ionophore, bis(pyridin-2-ylmethyl)amine. The sensor (PBITA) demonstrates a Zn(2+)-specific emission shift and enhancement with a 1:1 binding ratio. Due to the Zn(2+)-induced coplanation of 2-PBI via reversion/rotation, PBITA is shown to behave as a ratiometric sensor. The intracellular Zn(2+) imaging ability of the sensor has been tested in HeLa cells using a confocal microscope.
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Fabrication of water soluble and biocompatible CdSe nanoparticles in apoferritin with the aid of EDTA.
Dalton Trans
PUBLISHED: 01-23-2009
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Apoferritin-coated photoluminescent CdSe nanoparticles generated by an EDTA-mediated in situ method are photostable, water soluble and biocompatible.
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Molecular combo of photodynamic therapeutic agent silicon(iv) phthalocyanine and anticancer drug cisplatin.
Chem. Commun. (Camb.)
PUBLISHED: 01-19-2009
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The combination of a red light PDT agent and a Pt(ii)-based chemotherapeutic drug at the molecular level maintains the intrinsic functions of each unit; the conjugated complexes exhibit remarkable photocytoxicity and demonstrate potential to serve as agents for DNA-targeting PDT as well as red light photochemotherapy.
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Visible light excitable Zn2+ fluorescent sensor derived from an intramolecular charge transfer fluorophore and its in vitro and in vivo application.
J. Am. Chem. Soc.
PUBLISHED: 01-14-2009
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The UV- and sensor-induced interferences to living systems pose a barrier for in vivo Zn(2+) imaging. In this work, an intramolecular charge transfer (ICT) fluorophore of smaller aromatic plane, 4-amino-7-nitro-2,1,3-benzoxadiazole, was adopted to construct visible light excited fluorescent Zn(2+) sensor, NBD-TPEA. This sensor demonstrates a visible ICT absorption band, a large Stokes shift, and biocompatibility. It emits weakly (Phi = 0.003) without pH dependence at pH 7.1-10.1, and the lambda(ex) and lambda(em) are 469 (epsilon(469) = 2.1 x 10(4) M(-1) cm(-1)) and 550 nm, respectively. The NBD-TPEA displays distinct selective Zn(2+)-amplified fluorescence (Phi = 0.046, epsilon(469) = 1.4 x 10(4) M(-1) cm(-1)) with emission shift from 550 to 534 nm, which can be ascribed to the synergic Zn(2+) coordination by the outer bis(pyridin-2-ylmethyl)amine (BPA) and 4-amine. The Zn(2+) binding ratio of NBD-TPEA is 1:1. By comparison with its analogues NBD-BPA and NBD-PMA, which have no Zn(2+) affinity, the outer BPA in NBD-TPEA should be responsible for the Zn(2+)-induced photoinduced electron transfer blockage as well as for the enhanced Zn(2+) binding ability of 4-amine. Successful intracellular Zn(2+) imaging on living cells with NBD-TPEA staining exhibited a preferential accumulation at lysosome and Golgi with dual excitability at either 458 or 488 nm. The intact in vivo Zn(2+) fluorescence imaging on zebrafish embryo or larva stained with NBD-TPEA revealed two zygomorphic luminescent areas around its ventricle which could be related to the Zn(2+) storage for the zebrafish development. Moreover, high Zn(2+) concentration in the developing neuromasters of zebrafish can be visualized by confocal fluorescence imaging. This study demonstrates a novel strategy to construct visible light excited Zn(2+) fluorescent sensor based on ICT fluorophore other than xanthenone analogues. Current data show that NBD-TPEA staining can be a reliable approach for the intact in vivo Zn(2+) imaging of zebrafish larva as well as for the clarification of subcellular distribution of Zn(2+) in vitro.
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A porous metal-organic framework based on Zn6O2 clusters: chemical stability, gas adsorption properties and solvatochromic behavior.
Chem. Commun. (Camb.)
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A highly connected 3D metal-organic framework with tfz-d topology based on Zn(6)O(2) clusters and flexible carboxylate ligands has been synthesized. The obtained Zn-MOF shows solvatochromic behavior for fluorescence sensing of small molecules, gas adsorption properties and exceptional chemical stability and might have applications for separation and detection purposes.
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Parallel acoustic delay lines for photoacoustic tomography.
J Biomed Opt
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Achieving real-time photoacoustic (PA) tomography typically requires multi-element ultrasound transducer arrays and their associated multiple data acquisition (DAQ) electronics to receive PA waves simultaneously. We report the first demonstration of a photoacoustic tomography (PAT) system using optical fiber-based parallel acoustic delay lines (PADLs). By employing PADLs to introduce specific time delays, the PA signals (on the order of a few micro seconds) can be forced to arrive at the ultrasonic transducers at different times. As a result, time-delayed PA signals in multiple channels can be ultimately received and processed in a serial manner with a single-element transducer, followed by single-channel DAQ electronics. Our results show that an optically absorbing target in an optically scattering medium can be photoacoustically imaged using the newly developed PADL-based PAT system. Potentially, this approach could be adopted to significantly reduce the complexity and cost of ultrasonic array receiver systems.
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The role of vascular endothelial growth factor-D in diagnosis of lymphangioleiomyomatosis (LAM).
Respir Med
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Definite diagnosis of lymphangioleiomyomatosis (LAM) depends on either transbronchial lung biopsy or video-assisted thoracic surgery, unless there is a history of chylothorax, kidney angiomyolipoma (AML), or tuberous sclerosis complex (TSC). Vascular endothelial growth factor-D (VEGF-D) was recently considered as a novel diagnostic marker for LAM. Herein, we evaluated diagnostic value of serum VEGF-D in LAM patients.
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Targeting and delivery of platinum-based anticancer drugs.
Chem Soc Rev
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Platinum-based anticancer drugs occupy a crucial role in the treatment of various malignant tumours. However, the efficacy and applicability of platinum drugs are heavily restricted by severe systemic toxicities and drug resistance. Different drug targeting and delivery (DTD) strategies have been developed to prevent the shortcomings of platinum-based chemotherapy. These approaches can be roughly categorized into two groups; namely, active and passive tactics. Active DTD is realized through specific molecular interactions between the drugs and cell or tissue elements, while passive DTD is achieved by exploiting the enhanced permeability and retention effect in tumour tissues. The principal methods for active DTD include conjugation of platinum drugs with selective targeting moieties or encapsulation of platinum drugs in host molecules. Bioactive substances such as hormones, carbohydrates, bisphosphonates, peptides and proteins are commonly used in active DTD. Passive DTD generally involves the fabrication of functionalized polymers or nanoparticles and the subsequent conjugation of platinum drugs with such entities. Polymeric micelles, liposomes, nanotubes and nanoparticles are frequently used in passive DTD. In some cases, both active and passive mechanisms are involved in one DTD system. This review concentrates on various targeting and delivery techniques for improving the efficacy and reducing the side effects of platinum-based anticancer drugs. The content covers most of the related literatures published since 2006. These innovative tactics represent current state-of-the-art developments in platinum-based anticancer drugs.
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Multi-scale molecular photoacoustic tomography of gene expression.
PLoS ONE
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Photoacoustic tomography (PAT) is a molecular imaging technology. Unlike conventional reporter gene imaging, which is usually based on fluorescence, photoacoustic reporter gene imaging relies only on optical absorption. This work demonstrates several key merits of PAT using lacZ, one of the most widely used reporter genes in biology. We show that the expression of lacZ can be imaged by PAT as deep as 5.0 cm in biological tissue, with resolutions of ?1.0 mm and ?0.4 mm in the lateral and axial directions, respectively. We further demonstrate non-invasive, simultaneous imaging of a lacZ-expressing tumor and its surrounding microvasculature in vivo by dual-wavelength acoustic-resolution photoacoustic microscopy (AR-PAM), with a lateral resolution of 45 µm and an axial resolution of 15 µm. Finally, using optical-resolution photoacoustic microscopy (OR-PAM), we show intra-cellular localization of lacZ expression, with a lateral resolution of a fraction of a micron. These results suggest that PAT is a complementary tool to conventional optical fluorescence imaging of reporter genes for linking biological studies from the microscopic to the macroscopic scales.
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Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography.
J Biomed Opt
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With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.
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Design and synthesis of a ratiometric fluorescent chemosensor for Cu(II) with a fluorophore hybridization approach.
Org. Lett.
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A new ratiometric fluorescent sensor for Cu(2+), WLN, has been developed via integrating a 1,8-naphthalimide fluorophore with 8-aminoquinoline. WLN exhibits a highly selective ratiometric response to Cu(2+) over other transition metal ions in aqueous media. Moreover, its practical ratiometric imaging ability for intracellular Cu(2+) has been confirmed in human breast adenocarcinoma cells (MCF-7 cells) using a confocal microscope.
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An excitation ratiometric Zn2+ sensor with mitochondria-targetability for monitoring of mitochondrial Zn2+ release upon different stimulations.
Chem. Commun. (Camb.)
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A mitochondria-targeted fluorescent sensor (Mito-ST), constructed by integrating a sulfamoylbenzoxadiazole fluorophore with a phosphonium group, displays the specific Zn(2+)-induced hypsochromic shifts of both excitation (69 nm) and emission (35 nm) maxima. Its ratiometric Zn(2+) imaging ability via dual excitation mode has been applied in MCF-7 cells to clarify the different behaviours of mitochondrial Zn(2+) release stimulated by H(2)O(2) and SNOC.
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A microporous metal-organic framework with FeS(2) topology based on [Zn6(?6-O)] cluster for reversible sensing of small molecules.
Chem. Commun. (Camb.)
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The first luminescent metal-organic framework (MOF) with [Zn(6)(?(6)-O)] cluster has been synthesized and realized for reversible sensing of small molecules.
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Aberration correction for transcranial photoacoustic tomography of primates employing adjunct image data.
J Biomed Opt
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A challenge in photoacoustic tomography (PAT) brain imaging is to compensate for aberrations in the measured photoacoustic data due to their propagation through the skull. By use of information regarding the skull morphology and composition obtained from adjunct x-ray computed tomography image data, we developed a subject-specific imaging model that accounts for such aberrations. A time-reversal-based reconstruction algorithm was employed with this model for image reconstruction. The image reconstruction methodology was evaluated in experimental studies involving phantoms and monkey heads. The results establish that our reconstruction methodology can effectively compensate for skull-induced acoustic aberrations and improve image fidelity in transcranial PAT.
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Quantitative photoacoustic microscopy of optical absorption coefficients from acoustic spectra in the optical diffusive regime.
J Biomed Opt
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Photoacoustic (PA) microscopy (PAM) can image optical absorption contrast with ultrasonic spatial resolution in the optical diffusive regime. Conventionally, accurate quantification in PAM requires knowledge of the optical fluence attenuation, acoustic pressure attenuation, and detection bandwidth. We circumvent this requirement by quantifying the optical absorption coefficients from the acoustic spectra of PA signals acquired at multiple optical wavelengths. With the acoustic spectral method, the absorption coefficients of an oxygenated bovine blood phantom at 560, 565, 570, and 575 nm were quantified with errors of <3%. We also quantified the total hemoglobin concentration and hemoglobin oxygen saturation in a live mouse. Compared with the conventional amplitude method, the acoustic spectral method provides greater quantification accuracy in the optical diffusive regime. The limitations of the acoustic spectral method was also discussed.
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In vivo three-dimensional photoacoustic imaging based on a clinical matrix array ultrasound probe.
J Biomed Opt
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We present an integrated photoacoustic and ultrasonic three-dimensional (3-D) volumetric imaging system based on a two-dimensional (2-D) matrix array ultrasound probe. A wavelength-tunable dye laser pumped by a Q-switched Nd:YAG laser serves as the light source and a modified commercial ultrasound imaging system (iU22, Philips Healthcare) with a 2-D array transducer (X7-2, Philips Healthcare) detects both the pulse-echo ultrasound and photoacoustic signals. A multichannel data acquisition system acquires the RF channel data. The imaging system enables rendering of co-registered 3-D ultrasound and photoacoustic images without mechanical scanning. The resolution along the azimuth, elevation, and axial direction are measured to be 0.69, 0.90 and 0.84 mm for photoacoustic imaging. In vivo 3-D photoacoustic mapping of the sentinel lymph node was demonstrated in a rat model using methylene blue dye. These results highlight the clinical potential of 3-D PA imaging for identification of sentinel lymph nodes for cancer staging in humans.
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Whole-body ring-shaped confocal photoacoustic computed tomography of small animals in vivo.
J Biomed Opt
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We report a novel small-animal whole-body imaging system called ring-shaped confocal photoacoustic computed tomography (RC-PACT). RC-PACT is based on a confocal design of free-space ring-shaped light illumination and 512-element full-ring ultrasonic array signal detection. The free-space light illumination maximizes the light delivery efficiency, and the full-ring signal detection ensures a full two-dimensional view aperture for accurate image reconstruction. Using cylindrically focused array elements, RC-PACT can image a thin cross section with 0.10 to 0.25 mm in-plane resolutions and 1.6? s/frame acquisition time. By translating the mouse along the elevational direction, RC-PACT provides a series of cross-sectional images of the brain, liver, kidneys, and bladder.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.