Search PubMed⌕ Search

Biomedical subjects

Qun Chen

Publications and source records attributed to Qun Chen.

At least 37 records · Page 2Linked to original sources

Detection of caspase-3 activation in single cells by fluorescence resonance energy transfer during photodynamic therapy induced apoptosis.

In many apoptosis pathways, activation of caspase-3 is considered the final stage. In this study, we studied PDT induced caspase-3 activation with fluorescence resonance energy transfer (FRET) technique. A recombinant caspase-3 substrate, SCAT3, was used as the FRET probe. FRET fluorescence images were collected after PDT or TNF-alpha induced apoptosis. By analyzing the dynamic changes of FRET fluorescence, the results indicate that the caspase-3 activation started immediately after the PDT treatment. In contrast, FRET disruption caused by caspase-3 activation started at 3h after TNF-alpha treatment, due to different signaling pathway. The results have proofed, for the first time, that FRET is a sensitive technique that can be used to investigate PDT-induced activation of caspase-3 in real-time and in single cells. By choosing appropriate recombinant substrates as FRET probes, it is likely that FRET technique will provide a new real-time means to study the mechanism of PDT at single cell level.

Adenocarcinoma↗

Studies of a vascular-acting photosensitizer, Pd-bacteriopheophorbide (Tookad), in normal canine prostate and spontaneous canine prostate cancer.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) mediated with Tookad (Pd-bacteriopheophorbide, WST09) was investigated pre-clinically as part of a program to develop an alternative modality for treating prostate cancer. STUDY DESIGN/MATERIALS AND METHODS: Spontaneous canine prostate cancer and normal canine prostate were used as the animal models. Interstitial PDT was performed by IV infusion of the photosensitizer and irradiating the prostates with a diode laser (763 nm). The prostates were harvested 1-week post-PDT and subjected to histopathologic examinations. The effects of the drug doses and light doses were studied for one- and two-session PDT. Pharmacokinetics were studied using HPLC assay. The feasibility of using perfusing CT scans for assessing PDT lesions was also evaluated. RESULTS: Tookad is a vascular-acting drug and clears rapidly from the circulation. Tookad-PDT-induced lesions, in both normal and cancerous prostates, were characterized by marked hemorrhagic necrosis. CONCLUSIONS: Tookad-PDT is very effective in ablating prostatic tissue through its vascular effects.

Animals↗

Magnetic resonance imaging-based spirometry for regional assessment of pulmonary function.

In this work MRI-based spirometry is presented as a method for noninvasively assessing pulmonary mechanical function on a regional basis. A SPAMM tagging sequence was modified to allow continuous dynamic imaging of the lungs during respiration. A motion-tracking algorithm was developed to track material regions from time-resolved grid-tagged images. Experiments were performed to image the lungs during quiet breathing and volumetric strain was calculated from the measured displacement maps. Regional volume calculations, derived from volumetric strain, were integrated over the entire lung and compared to segmented volume calculations with good agreement. Results from this work demonstrate that MRI spirometry has the potential to become a clinically useful tool for measuring regional ventilation and assessing pulmonary diseases that regionally affect the mechanical function of the lung.

Adult↗

New therapeutic approaches for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic polyarthritis leading to joint destruction and remarkable disability. Current therapies have various degrees of efficacy, but toxicity frequently limits their long-term use. Although the etiology of the disease remains unknown, our increasing knowledge of the mechanisms underlying pathogenic events in rheumatoid synovitis has enabled selective targeting of the pathogenic elements of disease. Several new drugs have recently been introduced for the treatment of RA. These include cyclooxygenase type 2 inhibitors, adhesion molecules, T cells, B cells, cytokine/receptor, chemokines, angiogenesis, oral tolerance antigens, costimulatory molecules, and new disease-modifying antirheumatic drugs. Continuing research into the pathogenesis of RA will undoubtedly identify even more effective therapeutic approaches for the management of this disease in the future. In conclusion, the proof of principle has been established that selective targeting of pathogenic elements of disease results in substantial improvement in signs and symptoms as well as disease progression. Improved efficacy is expected with more aggressive targeting of the pathogenic elements.

Antibodies, Monoclonal↗

Effects of photodynamic therapy on peripheral nerve: in situ compound-action potentials study in a canine model.

OBJECTIVE: Our aim is to investigate the effects of photodynamic therapy (PDT) on peripheral nerve conductivity. BACKGROUND DATA: Interstitial PDT has been demonstrated as a promising treatment modality for prostate cancer. However, the sensitivity of nerves, in the immediate vicinity of the prostate gland, to PDT procedures has not been studied. This study attempts to establish an in situ canine model to evaluate direct PDT effect on peripheral nerves. METHODS: PDT was performed by irradiating the cutaneous branches of the saphenous nerve at 763 nm with light doses of 50-200 J/cm2 after i.v. infusion of the photosensitizer Tookad (0-2 mg/kg). Evoked compound-action potentials (CAP) were recorded directly from the surface of the saphenous nerve. The latencies to onset and conduction velocities were determined during PDT and 1-week post-PDT. RESULTS: Nerve and surrounding tissue damage corresponded well with drug/light doses. With Tookad doses of 2 mg/kg, treatment with 50 J/cm2 induced little change in saphenous nerve conduction properties. However, treatment with 100 J/cm2 resulted in localized nerve injury and decreases in nerve conduction velocities, and treatment with 200 J/cm2 severely damaged the nerve. CONCLUSIONS: This canine model adequately demonstrates effects of Tookad PDT on peripheral nerves. Direct irradiation of 100-200 J/cm2 can alter nerve conduction and induce nerve damage. Therefore, possible side effects of interstitial PDT on the pelvic plexus need to be investigated in future studies.

Action Potentials↗

[Detection of Mobiluncus species by special primer amplification and 16S DNA sequence analysis].

Bacterial Vaginosis (BV), a microecological disease leaded by overgrowth of the vaginal bacteria, is one of the Polymicrobial Diseases. The close relationship between BV and Mobiluncus ssp. was recognized gradually. But it is difficult to get the pure culture of this anaerobic bacterium because of its rigorous requirement for growth conditions. The vaginal discharge came from the BV animal model--Rhesus monkey was cultured in anaerobic environment. The 16S rRNA gene was amplified and sequenced using mobiluncus-specific primers. Mobiluncus ssp, closely related to Mobiluncus mulieris, were detected, by comparing with the 16S rRNA genes in the GenBank.

Animals↗

Effect of protein kinase C on proliferation and apoptosis of T lymphocytes in idiopathic thrombocytopenic purpura children.

It is well-documented that T lymphocyte proliferation and apoptosis are abnormal in idiopathic thrombocytopenic purpura (ITP) children. However, the underlying regulation mechanisms especially in terms of signal transduction remain unknown. In this paper, we reported the changes of protein kinase C (PKC) activity in peripheral blood T lymphocytes and the effect of PKC on T lymphocyte proliferation and apoptosis. We demonstrated that in ITP children, the activator (PMA) and inhibitor (H-7) of PKC affected on T lymphocyte proliferation and apoptosis dramatically, but they altered little in healthy children. PKC activity was significantly enhanced in ITP children together with an increased expression of FasL on CD3+T, CD4+T and CD8+T cells, resulting in a positive correlation between PKC activity and the expression of FasL on T cells. While the PKC activity and the platelet count were negatively correlated. Taken together, our findings suggest that the PKC activation may enhance T lymphocytes activity, suppress T cell apoptosis and be involve in thrombocytes damage as a mechanism related to immune pathogenesis of ITP.

Adolescent↗

Effects of the surface chemistry of macroreticular adsorbents on the adsorption of 1-naphthol/1-naphthylamine mixtures from water.

The adsorption behaviors of 1-naphthol, 1-naphthylamine and 1-naphthol/1-naphthylamine mixtures in water over two macroreticular adsorbents were investigated in single or binary batch systems at 293 K, 303 K and 313 K respectively. All the adsorption isotherms in the studied systems can be adequately fitted by Langmuir model. In the case of aminated macroreticular adsorbent NDA103, 1-naphthol is adsorbed to a larger extent than 1-naphthylamine; while, the opposite trend is found for nonpolar macroreticular adsorbent NDA100. It is noteworthy that at higher temperature (303 K and 313 K), the total uptake amounts of 1-naphthol and 1-naphthylamine in all binary-component systems are obvious larger than the pure uptake amounts in single-component systems, which is presumably due to the cooperative effect primarily arisen from the hydrogen-bonding interaction between the loaded 1-naphthol and 1-naphthylamine molecules. The simultaneous adsorption systems were confirmed to be helpful to the selective adsorption towards 1-naphthol according to the larger selective index.

1-Naphthylamine↗

Polarization and apoptosis of T cell subsets in idiopathic thrombocytopenic purpura.

It is well-known that idiopathic thrombocytopenic purpura (ITP) is an acquired organ-specific autoimmune hemorrhagic disease and dysfunctional cellular immunity is considered important in the pathophysiology of ITP. However, polarization patterns and apoptosis profiles of T lymphocytes remain unclear. In this study, we investigated the polarization of T cell subsets, the expressions of apoptotic proteins Fas/FasL on the subsets and the level of anti-apoptotic gene bcl-2 and bax mRNA. It was demonstrated that the ratios of Th1/Th2 and Tc1/Tc2 in ITP children were increased obviously and that the average percentages were increased clearly for Th1 and Th2, but not for Tc1 and Tc2. In ITP children, the enhancing expressions were detected for FasL on Th1 and Tc1 and for Fas on Th2 and Tc2. With increasing level of bcl-2 mRNA and decreasing expression of bax mRNA in ITP children, the ratio of bcl-2/bax mRNA was improved obviously, which was positive correlated with the ratio of Th1/Th2. Taken together, our findings indicate that ITP is a Th1 predominant disease. This polarization pattern of T cell subsets might be related to the high ratio of bcl-2/bax mRNA and the abnormal expressions of Fas and FasL on T cell subsets.

Apoptosis↗

High sensitive approach for point mutation detection based on electrochemiluminescence.

An electrochemiluminescence-polymerase chain reaction (ECL-PCR) method for point mutation detection has been developed. The target is amplified using a tris (bipyridine) ruthenium (TBR)-labeled forward and a biotinylated reverse primer. The amplification products are digested with specific restriction enzyme, then captured onto streptavidin-coated paramagnetic beads, and detected by measuring the ECL signal of the TBR label. The established technique was further applied to detect a specific point mutation in H-ras oncogene in T24 cell line. The results show that the system has a low detection limit of 100 fmol and a linear range of more than 3 orders of magnitude for H-ras amplicon; the two genotypes can be reliably discriminated. In summary, the mutant specific ECL-PCR method can be used to detect a point mutation that creates or destroys a restriction site in any gene. It is useful in single nucleotide polymorphism (SNP) and mutation detection due to its safety, high sensitivity and simplicity.

Biomarkers, Tumor↗

A novel method for measuring photosynthesis using delayed fluorescence of chloroplast.

Photosynthesis is the most important chemical reaction in the world. The measurement of plant photosynthesis rate plays an important role in agriculture. Light-induced delayed fluorescence (DF) in plants is an intrinsic label of the efficiency of charge separation at P680 in photosystem II (PS II). In this paper, we have developed a biosensor that can accurately measure the plant photosynthesis ability by means of DF. Compared with common methods for measuring the photosynthesis rate based on consumption of CO2, the proposed technique can quantify the plant photosynthesis ability with less influence of the environment. The biosensor is an all-weather measuring instrument, it has its own illumination power and utilizes intrinsic DF as the measurement marker. The current investigation has revealed that, there is a good correspondence between the results measured by the biosensor and that by commercially available portable photosynthesis system under controlled conditions. We thus conclude that DF is an excellent marker for evaluating plant photosynthesis ability under its biological status with less interferences of the environment.

Biosensing Techniques↗

Blockade of electron transport during ischemia protects cardiac mitochondria.

Subsarcolemmal mitochondria sustain progressive damage during myocardial ischemia. Ischemia decreases the content of the mitochondrial phospholipid cardiolipin accompanied by a decrease in cytochrome c content and a diminished rate of oxidation through cytochrome oxidase. We propose that during ischemia mitochondria produce reactive oxygen species at sites in the electron transport chain proximal to cytochrome oxidase that contribute to the ischemic damage. Isolated, perfused rabbit hearts were treated with rotenone, an irreversible inhibitor of complex I in the proximal electron transport chain, immediately before ischemia. Rotenone pretreatment preserved the contents of cardiolipin and cytochrome c measured after 45 min of ischemia. The rate of oxidation through cytochrome oxidase also was improved in rotenone-treated hearts. Inhibition of the electron transport chain during ischemia lessens damage to mitochondria. Rotenone treatment of isolated subsarcolemmal mitochondria decreased the production of reactive oxygen species during the oxidation of complex I substrates. Thus, the limitation of electron flow during ischemia preserves cardiolipin content, cytochrome c content, and the rate of oxidation through cytochrome oxidase. The mitochondrial electron transport chain contributes to ischemic mitochondrial damage that in turn augments myocyte injury during subsequent reperfusion.

Animals↗

Photoacoustic and ultrasonic coimage with a linear transducer array.

A technique is developed to simultaneously acquire ultrasound and photoacoustic (PA) images based on a linear transducer array. The system uses conventional ultrasound for rapid identification of potential targets. After a target is identified, the ultrasound echo and PA signals can be simultaneously obtained with optimized excitation and a signal collection sequence. The corresponding ultrasound impedance and optical absorption images are reconstructed with a phase-controlled algorithm. The approach can effectively reduce the artifacts associated with a conventional filter backprojection algorithm used in PA imaging by linear scanning. The technique provides a new approach for practical applications.

Algorithms↗

Photoacoustic imaging with deconvolution algorithm.

The impulse response of the ultrasonic transducer used for detection is crucial for photoacoustic imaging with high resolution. We demonstrate a reconstruction method that allows the optical absorption distribution of a sample to be reconstructed without knowing the impulse response of the ultrasonic transducer. A convolution relationship between photoacoustic signals measured by an ultrasound transducer and optical absorption distribution is developed. Based on this theory, the projection of the optical absorption distribution of a sample can be obtained directly by deconvolving the recorded PA signal originating from a point source out of that from the sample. And a modified filtered back projection algorithm is used to reconstruct the optical absorption distribution. We constructed a photoacoustic imaging system to validate the reconstruction method and the experimental results demonstrated that the reconstructed images agreed well with the original phantom samples. The spatial resolution of the system reaches 0.3 mm.

Acoustics↗

Fast photoacoustic imaging system based on 320-element linear transducer array.

A fast photoacoustic (PA) imaging system, based on a 320-transducer linear array, was developed and tested on a tissue phantom. To reconstruct a test tomographic image, 64 time-domain PA signals were acquired from a tissue phantom with embedded light-absorption targets. A signal acquisition was accomplished by utilizing 11 phase-controlled sub-arrays, each consisting of four transducers. The results show that the system can rapidly map the optical absorption of a tissue phantom and effectively detect the embedded light-absorbing target. By utilizing the multi-element linear transducer array and phase-controlled imaging algorithm, we thus can acquire PA tomography more efficiently, compared to other existing technology and algorithms. The methodology and equipment thus provide a rapid and reliable approach to PA imaging that may have potential applications in noninvasive imaging and clinic diagnosis.

Acoustics↗

Negative inotropic drugs alter indexes of cytosolic [Ca(2+)]-left ventricular pressure relationships after ischemia.

Negative inotropic agents may differentially modulate indexes of cytosolic [Ca(2+)]-left ventricular (LV) pressure (LVP) relationships when given before and after ischemia. We measured and calculated [Ca(2+)], LVP, velocity ratios [[(d[Ca(2+)]/dt(max))/(dLVP/dt(max)); VR(max)] and [(d[Ca(2+)]/dt(min))/(dLVP/dt(min)); VR(min)]], and area ratio (AR; area [Ca(2+)]/area LVP per beat) before and after global ischemia in guinea pig isolated hearts. Ca(2+) transients were recorded by indo 1-AM fluorescence via a fiberoptic probe placed at the LV free wall. [Ca(2+)]-LVP loops were acquired by plotting LVP as a function of [Ca(2+)] at multiple time points during the cardiac cycle. Hearts were perfused with bimakalim, 2,3-butanedione monoxime (BDM), nifedipine, or lidocaine before and after 30 min of ischemia. Before ischemia, each drug depressed LVP, but only nifedipine decreased both LVP and [Ca(2+)] with a downward and leftward shift of the [Ca(2+)]-LVP loop. After ischemia, each drug depressed LVP and [Ca(2+)] with a downward and leftward shift of the [Ca(2+)]-LVP loop. Each drug except BDM decreased d[Ca(2+)]/dt(max); nifedipine decreased d[Ca(2+)]/dt(min), whereas lidocaine increased it, and bimakalim and BDM had no effect on d[Ca(2+)]/dt(min). Each drug except bimakalim increased VR(max) and VR(min) before ischemia; after ischemia, only BDM and nifedipine increased VR(max) and VR(min). Before and after ischemia, BDM and nifedipine increased AR, whereas lidocaine and bimakalim had no effect. At 30 min of reperfusion, control hearts exhibited marked Ca(2+) overload and depressed LVP. In each drug-pretreated group Ca(2+) overload was reduced on reperfusion, but only the group pretreated with nifedipine exhibited both higher LVP and lower [Ca(2+)]. These results show that negative inotropic drugs are less capable of reducing [Ca(2+)] after ischemia so that there is a relatively larger Ca(2+) expenditure for contraction/relaxation after ischemia than before ischemia. Moreover, the differential effects of pretreatment with negative inotropic drugs on [Ca(2+)]-LVP relationships after ischemia suggest that these drugs, especially nifedipine, can elicit cardiac preconditioning.

Animals↗

Ischemia, rather than reperfusion, inhibits respiration through cytochrome oxidase in the isolated, perfused rabbit heart: role of cardiolipin.

Ischemia and reperfusion result in mitochondrial dysfunction, with decreases in oxidative capacity, loss of cytochrome c, and generation of reactive oxygen species. During ischemia of the isolated perfused rabbit heart, subsarcolemmal mitochondria, located beneath the plasma membrane, sustain a loss of the phospholipid cardiolipin, with decreases in oxidative metabolism through cytochrome oxidase and the loss of cytochrome c. We asked whether additional injury to the distal electron chain involving cardiolipin with loss of cytochrome c and cytochrome oxidase occurs during reperfusion. Reperfusion did not lead to additional damage in the distal electron transport chain. Oxidation through cytochrome oxidase and the content of cytochrome c did not further decrease during reperfusion. Thus injury to cardiolipin, cytochrome c, and cytochrome oxidase occurs during ischemia rather than during reperfusion. The ischemic injury leads to persistent defects in oxidative function during the early reperfusion period. The decrease in cardiolipin content accompanied by persistent decrements in the content of cytochrome c and oxidation through cytochrome oxidase is a potential mechanism of additional myocyte injury during reperfusion.

Animals↗

Supramolecular self-assembly of inclusion complexes of a multiarm hyperbranched polyether with cyclodextrins.

A new class of crystalline inclusion complexes of a multiarm hyperbranched polyether combined with various cyclodextrins (CDs) was successfully prepared. Using self-condensing ring-opening polymerization, a kind of multiarm polyether with a hyperbranched poly(3-ethyl-3-oxetanemethanol) core and multiple linear poly(ethylene glycol) (PEG) arms was obtained. It has been found that this kind of hyperbranched polyether can be dissolved in water. Adding alpha-CDs to the multiarm hyperbranched polyether solution, molecular recognition results in the formation of crystalline inclusion complexes based on the noncovalent interactions between the linear PEG arms of the polyether particles and the alpha-CDs. These multiarm polyether inclusion complexes have been well characterized. Interestingly, quite different from inclusion complexes of CDs and linear polymeric guests, the complexes of the multiarm hyperbranched polyether with alpha-CDs show a novel lamellar morphology. The experimental results validate that the resultant lamellar crystals have a juxtaposed structure. In addition, the formation mechanism of these inclusion complexes of a multiarm polyether with alpha-CDs has also been well described. Besides the role of displacement of associated water molecules and the presence of hydrogen bonding between CDs in channel structure CD inclusion complexes, the noncovalent intermolecular forces between CDs and polymers also play an important role in the formation of complex architectures.

Cyclodextrins↗