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Biomedical subjects

Bo Liu

Publications and source records attributed to Bo Liu.

At least 181 records · Page 10Linked to original sources

A new ruthenium-catalyzed hydrogen-transfer reaction: transformation of 3-benzyl but-1-ynyl ethers into 1,3-dienes and benzaldehyde.

We report a ruthenium-catalyzed reaction for various 3-benzyl but-1-ynyl ethers with suitable functionalities. Treatment of these substrates with TpRu(PPh3)(CH3CN)2PF6 (8.0 mol %) catalyst in 1,2-dichloroethane (80 degrees C, 12 h) afforded functionalized 1,3-dienes and benzyl aldehyde in good yields. This process is considered to be a tandem dealkoxylation and transfer hydrogenation. Deuterium-labeling experiments reveal that the migration of different hydrogen atoms proceeds regiospecifically. A plausible mechanism is proposed on the basis of the results of isotope experiment.

Journal Article↗

Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 6. Structure-activity studies of orally bioavailable, 2-pyridone-containing peptidomimetics.

The structure-based design, chemical synthesis, and biological evaluation of various 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of a peptidomimetic binding determinant and a Michael acceptor moiety, which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The 2-pyridone-containing inhibitors typically display improved 3CP inhibition properties relative to related peptide-derived molecules along with more favorable antiviral properties. The cocrystal structure of one pyridone-derived 3CP inhibitor complexed with HRV-2 3CP is also described along with certain ab initio conformation analyses. Optimization of the 2-pyridone-containing compounds is shown to provide several highly active 3CP inhibitors (k(obs)/[I] > 500,00 M(-1) s(-1)) that function as potent antirhinoviral agents (EC(50) = <0.05 microM) against multiple virus serotypes in cell culture. One 2-pyridone-containing 3CP inhibitor is shown to be bioavailable in the dog after oral dosing (F = 48%).

3C Viral Proteases↗

Toward synthetic transcription activators: recruitment of transcription factors to DNA by a PNA-peptide chimera.

A PNA-peptide chimera designed to mimic the biochemical function of transcription activators has been synthesized and characterized. The bis-PNA segment binds specifically to a DNA site while the 20-residue peptide is capable of binding to the transcription factors Gal11 and Gal80. The PNA-peptide chimera thus mimics one of the central functions of a native transcription activator, recruitment of transcription factors to a specific DNA site.

DNA↗

Down-regulation of the ERK1 and ERK2 mitogen-activated protein kinases using antisense oligonucleotides inhibits intimal hyperplasia in a porcine model of coronary balloon angioplasty.

OBJECTIVE: Neointimal hyperplasia is a central feature in the pathogenesis of a variety of vascular pathologies. Mitogen-activated protein kinases (MAPK) are involved in the downstream transduction of signals from receptors for many of the molecules known to be instrumental in this process and thus represent a potential target for the modification of the proliferative response. We examined the hypothesis that down-regulation of MAPK would inhibit neointima formation in a porcine coronary injury model. METHODS: Balloon angioplasty was performed on 38 coronary arteries from 23 large white pigs. Antisense oligonucleotides to the p42 and p44 MAPK were locally delivered to the site of injury immediately after balloon injury. At 7 or 21 days, arteries were harvested for morphometry, determination of cell proliferation and assessment of MAPK protein levels. RESULTS: At 7 days, neointima formation was significantly reduced compared to controls (corrected intima/media ratio (IMR) 1.01+/-0.13 vs. 1.61+/-0.07, P<0.01) and this was associated with a 58% and 23% down-regulation of p42 and p44 protein levels, respectively. Intimal and medial proliferation rates were also reduced by 32% and 26%, respectively. At 21 days however, the effect of the treatment on MAPK protein levels was no longer significant and this correlated with a loss of the effects on IMR and cell proliferation. CONCLUSIONS: Down-regulation of MAPK inhibits early smooth muscle cell (SMC) proliferation and neointimal thickening in response to arterial injury, implying that it plays an important role in determining the early vascular response to injury. Inhibitory effects were less apparent at 21 days after a single delivery of oligonucleotide, implying that more sustained local delivery may be required to achieve longer term therapeutic benefit.

Angioplasty, Balloon, Coronary↗

Impact of fusion avoidance on performance of the automatic threshold tracking feature in dual chamber pacemakers: a multicenter prospective randomized study.

The Autocapture algorithm enables automatic capture verification on a beat-by-beat basis by recognizing the evoked response signal following each pacemaker stimulus. The algorithm intends to increase patient safety while decreasing energy consumption. However, the occurrence of fusion beats, particularly during dual chamber pacing, may limit the energy saving effect of Autocapture. The aim of this multicenter, prospective, randomized study was to evaluate the impact of the Fusion Avoidance (FA) algorithm on the incidence of fusion beats. Thirty-eight patients (mean age 69 +/- 13 years) with intrinsic AV conduction who were implanted with an Affinity DR were studied. After programming a PV/AV delay of 120/190 ms, patients were randomized to FA On or Off. Each group was further randomized with respect to activation of the AutoIntrinsic Conduction Search (AICS) algorithm. The total number of beats, ventricular paced beats, fusion beats, backup pulses, and threshold searches were analyzed from 24-hour Holter recordings. The number of total beats was comparable in both FA groups. The number of total ventricular paced beats, fusion beats, backup pulses, and threshold searches were significantly reduced in the FA On group (% reduction: 68% P < 0.001, 75% P < 0.01, 95% P < 0.01, and 94% P < 0.05, respectively). The number of ventricular paced beats with full capture was significantly reduced when AICS was activated (P < 0.05). In conclusion, the FA algorithm substantially reduces the amount of ventricular paced beats, fusion beats, unnecessary backup pulses and threshold searches, and therefore, provides added benefits in energy saving obtained by Autocapture.

Aged↗

The signaling protein Rho is necessary for vascular smooth muscle migration and survival but not for proliferation.

BACKGROUND: The small GTPase Rho has been implicated in a variety of cellular processes. Vascular smooth muscle cell (SMC) migration, proliferation, and apoptosis are important events that contribute to the formation of intimal hyperplasia. To better understand the importance of Rho in intimal hyperplasia, we evaluated the necessity of Rho for these 3 cellular processes. METHODS: We used for these studies a recombinant C3 exoenzyme (C3), which selectively adenosine diphosphate-ribosylates and, thus, functionally inactivates Rho. SMC migration was determined by scratch and modified Boyden chamber assays, proliferation by tritiated-thymidine incorporation, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. RESULTS: Pretreatment of human SMC with C3 overnight resulted in adenosine diphosphate-ribosylation and inactivation of Rho. Inactivation of Rho completely eliminated SMC migration in response to platelet-derived growth factor (PDGF)-AB. Furthermore, C3 blocked phosphorylation of focal adhesion kinase, tensin, and paxillin, which are essential for cellular migration. In contrast, C3 did not significantly affect DNA synthesis in response to PDGF-AB or activation of mitogen-activated protein kinase, a signaling mediator of PDGF-stimulated proliferation. However, prolonged inactivation of Rho by C3 induced apoptosis of SMC. CONCLUSIONS: The small GTPase Rho is necessary for vascular SMC migration and cell survival but not for proliferation. Manipulation of Rho might have therapeutic value in modulating intimal hyperplasia.

ADP Ribose Transferases↗

Formation of protoplasts from cultured tobacco cells and Arabidopsis thaliana by the action of cellulosomes and pectate lyase from Clostridium cellulovorans.

The crude culture supernatants from Clostridium cellulovorans were tested for their ability to convert plant cells to protoplasts. The supernatants readily released protoplasts from cultured tobacco cells and Arabidopsis thaliana. The crude culture supernatant from pectin-grown cells was more active than supernatants from glucose-, cellobiose-, xylan-, and locust bean gum-grown cells. After removal of cellulosomes, the crude culture supernatant lost its protoplast formation activity. The protoplast formation activity of the crude culture supernatant from C. cellulovorans was more effective than those of commercial enzymes based on protein content.

Arabidopsis↗

[Study of noninvasive measurement of venous pressure].

A new device that allows noninvasive measurement of venous pressure has been invented in our laboratory and tested for its feasibility and validity. The device consists of four parts: 1. the air infusion system; 2. the pressure sensor gauge; 3. signal transducer and data processing system 4. the fixing apparatus. The correlation between noninvasive pressure and invasive pressure has been studied in vitro test on a saphenous vein model and in vitro test on dog's portal venous system. In vitro and vivo study, an excellent correlation between noninvasive pressure and invasive pressure was obtained(r = 0.99, P < 0.0005; r = 0.97, P < 0.005). These data suggest that the new device allows a noninvasive measurement of venous pressure especially for the large veins such as vena cava, venae pulmonales and esophageal varices.

Animals↗

Functional recovery of the spinal cord following ischemia and reperfusion injury.

OBJECTIVE: To study the changes of excitatory amino acids (EAAs) and intracellular calcium ([Ca2+]i), and the protective effect of EAAs receptor antagonists in the tissues of rabbit lumbar spinal cord after 40-minues ischemia and 4-hours reperfusion. METHODS: Thirty healthy rabbits were divided into six groups: sham-operation, 40-minues ischemia, 4-hour reperfusion, ketamine and MgSO4 treatment, ketamine treatment, and saline treatment groups. The contents of EAAs (glutamate and aspartate) and [Ca2+]i were measured. RESULTS: The contents of glutamate and aspartate were decreased to 15.18 micromol/g+/-2.33 micromol/g and 9.99 micromol/g+/-0.69 micromol/g, respectively; 13.75 micromol/g+/-2.58 micromol/g and 6.49 micromol/g+/-1.39 micromol/g after reperfusion. In the ischemia group, the [Ca2+]i was elevated to 221.2 microg/g+/-4.27 microg/g, and elevated further to 298.3 microg/g+/-9.26 microg/g after reperfusion, being significantly higher than that of ischemia and control groups. Ketamine could obviously increase the level of glutamate and aspartate and decrease the level of [Ca2+]i during the ischemia and reperfusion injury. CONCLUSIONS: The excitotoxicity of EAAs and the overload of calcium induced by EAAs play a harmful role in ischemia and reperfusion injury. Ketamine has an effective inhibitory effect.

Animals↗

Calculation of esophageal variceal wall tension by ultrasonic microprobe and noninvasive pressure measurements.

OBJECTIVE: To calculate esophageal variceal wall tension by sonographic and noninvasive pressure measurements and to study the role of esophageal variceal wall tension in predicting the likelihood of esophageal variceal rupture. METHODS: In 28 patients with esophageal varices, a 20 MHz ultrasonographic transducer was used to image esophageal varices; the radius and wall thickness of the varices were calculated. Esophageal variceal pressure measurements were obtained noninvasively. The correlation between the esophageal wall tension and esophageal variceal pressure gradient were studied. RESULTS: There was a linear correlation between the esophageal wall tension and the variceal pressure gradient after curve fitting (r=0.87, p < 0.05). CONCLUSION: Esophageal variceal wall tension is an important parameter in predicting variceal rupture.

Adult↗

[Characteristics of perioperative lumbar operation for the elderly].

OBJECTIVES: To study the characteristics of senile patients during perioperative lumbar operation and discuss matched surgical method. METHODS: From 1998 to 2000, lumbar operations were performed in 41 elderly patients (average age 68). 14 patients had lumbar disc herniation, 11 lumbar disc herniation with lumbar spinal stenosis, 12 lumbar instability and spondylolisthesis, 2 reoperation, and 2 combined compression of cervicle and thoracic spinal cord. RESULTS: Many patients were complicated by the following diseases: hypertension (14), coronary heart disease (9), diabetes mellitus (4), cerebral infarction (3), rheumatic heart disease (1), pulmonary heart disease (1), and complicated with 2 or 3 diseases (9). Discectomy was performed in 14 patients, decompression + discectomy in 11, posterior lateral fusion with pedicle instrument in 9, posterior lateral intravertebrae fusion with instrument in 3. Fixation of 2 levels was made in 5 patients, 3 levels in 3, and multi-levels in 2. Postoperation JOA amelioration rate was 81.6%. CONCLUSION: The condition of adjacent segment should be considered in the operative treatment of elderly patients. Caution should also be taken to coexisting diseases.

Aged↗

[Establishment and characterization of human extrahepatic growing hepatocellular carcinoma cell line EGHC-9901].

OBJECTIVE: To establish a new extrahepatic growing hepatocellular carcinoma cell line. METHODS: A specimen from extrahepatic growing hepatocellular carcinoma was cultured in vitro. Cancer cells were studied morphologically and subjected to karyotype analysis, DNA analysis, and tumor formation evaluation. RESULTS: Morphological observation and functional analysis showed that their features were similar to those of HCC. Chromosomes with a variation of 76 approximately 104 were able to secret AFP in vitro and to form bile canaliculi with microvilli. CONCLUSION: EGHC-9901 cell line has characteristics of the extrahepatic growing hepatocellular carcinoma.

Adult↗

[Effects of laser in situ keratomileusis (LASIK) retreatment on the central corneal endothelium and retina and optic nerve].

OBJECTIVE: To investigate the effects of laser in situ keratomileusis (LASIK) on the corneal endothelium, retina and optic nerve for correcting residual myopia caused by undercorrection or regression. METHODS: The pre- and post-operative values of central corneal endothelium and electrophysiological functions of retina and optic nerve were analyzed respectively in 23 eyes of 18 patients who received LASIK retreatment. The endothelium checked by contact specular microscopy was analyzed for central cell density (CCD), coefficient of cell variation in size and hexagonality preoperatively and 1, 4, 12 weeks after the operation. The amplitude and latency of P(100) in standard pattern visual evoked potentials (P-VEPs), that of a, b waves of different reactions in flash electroretinograms (F-ERGs) and also the total amplitude of oscillatory potentials (OPs) were evaluated preoperatively and 2, 12 weeks after the operation. RESULTS: The mean CCD decreased significantly (3.94%) one week after the operation (P < 0.01). The change was negatively correlated with the thickness of residual untreated posterior cornea (r = -0.719, P < 0.01) and not significantly correlated with the amount of laser pulse (r = 0.371, P > 0.05). There was no significant difference between preoperative and either 4 or 12 week postoperative CCD (P > 0.05). No significant differences in mean coefficient variation and hexagonality were found between preoperative and postoperative values in the follow up (P > 0.05). Examination of electrophysiological function showed that the amplitude of P(100) increased and the latency of P(100) decreased 2 and 12 weeks postoperatively. The significant changes were only at spatial frequency 34' in the P-VEPs test (P < 0.05). In F-ERGs test, there was no significant change in amplitude, latency of a, b waves or total amplitude of OPs between pre-operative and either 2 or 12 week post-operative values (P > 0.05). CONCLUSIONS: Retreatment after LASIK may cause a reversible reduction of CCD with no morphological changes in a short period (1 week) after the operation. It was not absolutely safe for corneal endothelium when the thickness of residual untreated basal cornea approaches to 200 micro m. These results show that the operation seems not to cause functional impairment in the retina and optic nerve. And it also can improve the quality of vision for some degrees.

Adult↗

[Comparison of neural response telemetry thresholds with behavioral T/C levels].

OBJECTIVE: To provide an objective method to estimate T-levels and C-levels using neural response telemetry (NRT) thresholds for children, from whom we can not get accurate responses because they are very young or have other disabilities, by comparing NRT thresholds and T/C levels. METHODS: Seventy patients implanted with the nucleus CI24M multiple cochlear implant system participated in this study. 329 electrodes were tested. The software used in this study was NRT 2.04. Monopolar stimulation mode was used during NRT threshold measurement. No. 3, 5, 10, 15, 20 electrodes were tested for each patient. The T-levels and C-levels were obtained at the same visit. RESULTS: 92.7% of all the tested electrodes recorded NRT responses. There were variations in the amplitudes and thresholds of NRT responses across subjects and electrodes. NRT thresholds fell within the different points of the MAP dynamic range. The mean of NRT thresholds was shown to fall between the mean of T-levels and C-levels. The NRT thresholds and T/C levels reduced from basal to apical ends of the cochlear. CONCLUSIONS: Considerable variability across subjects was noted. So it is difficult to estimate T-levels and C-levels accurately by testing only NRT thresholds only. NRT technology provides a new objective method for estimating T-levels and C-levels for children who are unable to cooperate with audiologists during mapping after operation. The new NRT technology should be improved in the future.

Adolescent↗

Equilibrium Acidities and Homolytic Bond Dissociation Enthalpies of the Acidic C-H Bonds in As-Substituted Triphenylarsonium and Related Cations(1).

Equilibrium acidities (pK(HA)s) of As-fluorenyltriphenylarsonium, As-phenacyltriphenylarsonium, six As-(para-substituted benzyl)triphenylarsonium [p-GC(6)H(4)CH(2)(+)AsPh(3)] (G = H, Me, CF(3), CO(2)Me, CN, and NO(2)), and six P-(para-substituted benzyl)tri(n-butyl)phosphonium [p-GC(6)H(4)CH(2)(+)P(n-Bu)(3)] (G = H, Me, CF(3), CO(2)Me, CN, and NO(2)) bromide salts, together with the oxidation potentials [E(ox)(A(-))] of their conjugate bases (ylides) have been determined in dimethyl sulfoxide (DMSO) solution. Introduction of an alpha-triphenylarsonium (alpha-Ph(3)As(+)) group was found to increase the adjacent C-H bond acidities by 13-20 pK units (18-27 kcal/mol). The equilibrium acidities for the two series p-GC(6)H(4)CH(2)(+)AsPh(3) and p-GC(6)H(4)CH(2)(+)P(n-Bu)(3) cations were found to be nicely correlated with the Hammett sigma(-) constants of the corresponding para-substituents (G) (Figures 1 and 2). The homolytic bond dissociation enthalpies (BDEs) of the acidic C-H bonds determined by using eq 1 reveal that an alpha-Ph(3)As(+) group increases the BDE value of the adjacent acidic C-H bond by 2-5 kcal/mol, whereas the substituent effects for an alpha-Ph(3)P(+) or alpha-(n-Bu)(3)P(+) group was found to be dependent on the nature of the substituents attached to the alpha-carbon atom. Good linear correlations were obtained for the equilibrium acidities of As-(para-substituted benzyl)triphenylarsonium and P-(para-substituted benzyl)tri(n-butyl)phosphonium cations with the oxidation potentials of their conjugate bases (ylides) as shown in Figures 3 and 4, respectively.

Journal Article↗

Tetragonal Crystal Structure of Mung Bean Inhibitor-porcine Trypsin Complex.

Crystal structure of the mung bean inhibitor-porcine trypsin (1:2) ternary complex in the tetragonal crystal with space group I422 was determined at 0.25nm resolution. 56 residues of the mung bean inhibitor were resolved among which one more residue Pro11 was determined than the previously reported structure in the trigonal crystal of the same complex. The structure of the inhibitor in the tetragonal crystal is similar to that in the trigonal crystal and the complexes in tetragonal crystal is also in packing disorder as in trigonal crystal, i.e., the complexes pack in two orientations Ta : MaMb : Tb and Tb : MbMa : Ta(Ta, Tb=trypsin, Ma, Mb=loop I and loop II of mung bean inhibitor respectively). But there are some differences in the two crystal forms. First, the inhibitor in the tetragonal crystal has no pseudo- beta-sheet structure which the trigonal crystal has. Second, its conformation is somewhat different from that in the trigonal crystal.Analysis showed that the linkage peptides between the two regid domains of the inhibitor were flexible, which also accounted for the formation of different crystal forms of this complex. Moreover, comparing mung bean inhibitor to other Bowman-Birk inhibitors showed that the two double-stranded antiparallel beta-sheets and the reactive binding loops were highly conservative.

Journal Article↗