Search PubMed⌕ Search

Biomedical subjects

L Wang

Publications and source records attributed to L Wang.

At least 415 records · Page 23Linked to original sources

Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

Adult C57BL/6 mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Intrastriatal transplantation of bone marrow stromal cells (MSCs) was performed 1 week after MPTP administration. MSCs were harvested from donor adult mice, and then cultured and prelabeled with bromodeoxyuridine (BrdU). MPTP-Parkinson's disease (PD) mice treated with intrastriatal injection of phosphate-buffered saline (PBS), and normal non-MPTP mice were used as controls. MPTP-PD mice with MSC intrastriatal transplantation exhibit significant improvement on the rotarod test (P<0.05) at day 35 compared with PBS controls. Immunohistochemistry shows that BrdU reactive cells survive in the transplanted areas in the MPTP-PD striatum at least 4 weeks after administration. Scattered BrdU reactive cells express tyrosine hydroxylase (TH) immunoreactivity. Our findings suggest that MSCs injected intrastriatally survive, express dopaminergic protein TH immunoreactivity, and promote functional recovery.

Animals↗

Environment, genome and cancer.

Cancer is one of the most serious diseases that threaten human being today. To some degree, it is a genetic disease but environmental and other nongenetic factors clearly play a role in many stages of neoplastic process. Genetic factors by themselves are thought to explain only about 5% of all cancer. The remainder can be attributed to external, 'environment' factors that act in conjunction with both genetic and acquired susceptibility. Of note, part of the susceptibility is owing to the variety of human genome. So, environment, human genome and cancer have much to do with each other. Combining all of the information from epidemiology and from research works in laboratory with policy-making and clinical works, purifying the environment, giving special protection to the high risk population, the mortality of cancer may decrease gradually in the future.

Carcinogens, Environmental↗

Neural activities during Wisconsin Card Sorting Test--MEG observation.

The present study recorded activities of magnetoencephalography (MEG) to the presentation of cards, and to the presentation of feedback signals in 12 normal subjects while they performed the Wisconsin Card Sorting Test (WCST), to observe temporal and spatial processing during the task. The MEG responses were compared between two different conditions in the presentation both of cards and of feedback signals: the cards proceeded by the first wrong [W1st(C)] and by the 4th correct feedback signals [C4th(C)]; and the feedback of the first wrong [W1st(FB)] and the 4th correct signals [C4th(FB)]. A multi-dipole model, brain electric source analysis (BESA), was used to explore the dipole sources responsible for the MEG activities. We found that MEG activity differences between the W1st(C) and the C4th(C) condition occurred in the period of 190-220 ms (M190 and M200), and 300-440 ms (M300 and M370) mainly at the supramarginal gyrus, the dorsolateral prefrontal, and the middle and inferior frontal gyrus. MEG differences between the W1st(FB) and the C4th(FB) condition occurred 460-640 ms (M460) after the presentation of the feedback signals, with the activation of the dorsolateral prefrontal cortex and the middle frontal cortex. No significant location differences were found between the frontal responses (M370) of the W1st(C) and M460 of the W1st(FB). Our results proved that the WCST task activates a broad frontal area and the parieto-frontal network across time streaming. Both shifting attention to the wrong feedback and enhanced visual working memory to the sorting shifting condition of the card presentation occur in the same areas at different time points.

Adult↗

Chemiluminescence flow sensor for berberine with immobilized reagents.

A sensitive chemiluminescence (CL) sensor for berberine combined with flow-injection (FI) technology is described. The analytical reagents involved in the CL reaction, including luminol and potassium ferricyanide, were both immobilized on an anion-exchange resin column. While a volume of sodium phosphate was passed through the column, the two CL reagents were eluted from the resin and then mixed with a berberine stream under alkaline conditions. By means of the fast oxidation reaction between berberine and potassium ferricyanide, potassium ferrocyanide was generated, which then inhibited the CL reaction of luminol and potassium ferricyanide. The decreased CL intensity was correlated with the berberine concentration in the range from 0.05 to 300 ng mL(-1 )with a relative standard deviation of less than 4.3%, and the limit of detection was 0.02 ng mL(-1) at a flow rate of 2.0 mL min(-1). It was shown that the flow sensor could greatly improve the selectivity and sensitivity for determination of berberine. The determination of analyte could be performed in 2 min, including sampling and washing and be stable for over 300 analyses. Some interference and additives in preparations were tested. Two herbal medicines commonly found in compound prescriptions, rutin and baicalin, were studied preliminarily. The method has been applied for the determination of berberine in pharmaceutical preparations successfully.

Berberine↗

[[(18)F]N-(4'-fluorobenzyl)-4-(3-bromophenyl) acetamide for imaging the sigma receptor status of tumors: comparison with [(18)F]FDG, and [(125)I]IUDR.

A series of biodistribution studies were conducted with the radiotracer, [(18)F]N-(4'-fluorobenzyl)-4-(3-bromophenyl)acetamide, [(18)F]1 in nude mice bearing tumor xenografts of the mouse mammary adenocarcinoma, line 66. This radiotracer has a high affinity for both sigma(1) and sigma(2) receptors. In vivo studies were also conducted in order to assess the effect of blocking sigma(1) receptors on tumor uptake and the tumor:background ratio of this radiotracer. The results of these studies revealed that blocking the sigma(1) receptor so that only the sigma(2) receptors are labeled in vivo, results in a higher tumor:background ratio with only a small reduction in the tumor uptake of the radiotracer relative to the no-carrier-added (i.e., nonselective) conditions. Comparative in vivo studies were also conducted with the anatomic and metabolic imaging agent, [(18)F]FDG, and a radiolabeled DNA precursor, [(125)I]IUdR. Both of these radiolabeled compounds represent classes of agents that have been proposed for imaging the proliferative status of solid tumors. The results of these studies indicated that a sigma(2)-selective imaging agent may be, 1) a better anatomic imaging agent for breast cancer than [(18)F]FDG, and 2) a better functional imaging agent than the radiolabeled DNA precursors, [(123/124)I]IUdR and [(11)C]thymidine, for measuring the proliferative status of breast tumors with PET and SPECT. However, additional studies will be needed to compare sigma(2)-selective imaging agents with [(18)F]FLT in order to determine which is the more appropriate imaging agent for measuring the proliferative status of breast tumors with PET.

Acetamides↗

A general approach for the generation of orthogonal tRNAs.

BACKGROUND: The addition of new amino acids to the genetic code of Escherichia coli requires an orthogonal suppressor tRNA that is uniquely acylated with a desired unnatural amino acid by an orthogonal aminoacyl-tRNA synthetase. A tRNA(Tyr)(CUA)-tyrosyl-tRNA synthetase pair imported from Methanococcus jannaschii can be used to generate such a pair. In vivo selections have been developed for selecting mutant suppressor tRNAs with enhanced orthogonality, which can be used to site-specifically incorporate unnatural amino acids into proteins in E. coli. RESULTS: A library of amber suppressor tRNAs derived from M. jannaschii tRNA(Tyr) was generated. tRNA(Tyr)(CUA)s that are substrates for endogenous E. coli aminoacyl-tRNA synthetases were deleted from the pool by a negative selection based on suppression of amber nonsense mutations in the barnase gene. The remaining tRNA(Tyr)(CUA)s were then selected for their ability to suppress amber nonsense codons in the beta-lactamase gene in the presence of the cognate M. jannaschii tyrosyl-tRNA synthetase (TyrRS). Four mutant suppressor tRNAs were selected that are poorer substrates for E. coli synthetases than M. jannaschii tRNA(Tyr)(CUA), but still can be charged efficiently by M. jannaschii TyrRS. CONCLUSIONS: The mutant suppressor tRNA(Tyr)(CUA) together with the M. jannaschii TyrRS is an excellent orthogonal tRNA-synthetase pair for the in vivo incorporation of unnatural amino acids into proteins. This general approach may be expanded to generate additional orthogonal tRNA-synthetase pairs as well as probe the interactions between tRNAs and their cognate synthetases.

Amino Acyl-tRNA Synthetases↗

Construction of a generic reaction knowledge base by reaction data mining.

As synthesis by combinatorial chemistry and high throughput screening have become well-established strategies in the drug discovery process, chemists face increased challenges in managing large amounts of data and using these data to design more diverse and focused libraries. As synthesis is an intuitive and empirical process, however, the classical approaches to computer-assisted synthesis planning do not fully satisfy the needs of the synthetic chemist. We describe a novel computational technique for extracting reaction data and building a generic reaction knowledge base (GRKB) to provide chemists with useful and well-organized knowledge. The method consists of three key steps: (1) the automatic recognition of reaction centers, (2) the definition of a hierarchy of reaction patterns, and (3) the organization of the generic reaction knowledge. Significant reaction knowledge has been discovered via mining a subset of the InfoChem Reaction database. A frame system has been constructed to store and retrieve the GRKB. Applications of this GRKB to synthesis planning are illustrated.

Artificial Intelligence↗

Molecular biology of Hendra and Nipah viruses.

The structure and genetic organization of Hendra and Nipah viruses places them in the subfamily Paramyxovirinae. However, low homology with other subfamily members and several novel biological and molecular features such as genome length and F(0 )cleavage site suggest classification in a new genus within the Paramyxovirinae.

Amino Acid Sequence↗

Raman and FTIR spectroscopies of fluorescein in solutions.

Raman and Fourier transform-infra red (FT-IR) spectroscopies of fluorescein in aqueous solutions have been investigated in the pH range from 9.1 to 5.4. At pH 9.1 fluorescein is in the dianion form. At pH 5.4, fluorescein is a mixture of monoanion (approximately 85%), dianion and neutral forms (together approximately 15%). The fluorescence quantum yield drops from 0.93 for the dianion form to 0.37 for the monoanion form. The Raman and FT-IR studies focused on the frequency range from 1000 to 1800 cm(-1) which contains the skeletal vibrational modes of the xanthene moiety of fluorescein. At pH 9.1, the spectroscopic feature of fluorescein dianion are consistent with a picture of an electron delocalized among the xanthene moiety and two identical oxygens attached to opposite ends of the xanthene moiety, forming a very symmetric structure. The characteristic of fluorescein dianion is the presence of the phenoxide-like stretch at 1310 cm(-1). At pH 5.4, fluorescein monoanion has lost the symmetric structure characteristic of the dianion. The spectra of the monoanion have distinctive contributions from the phenolic bend at 1184 cm(-1). The assignments of the vibrational bands shown in Raman and FT-IR spectra are given based on both literature and the ab initio calculations at the Hartree-Fock level with HF/6-31 + +G* basis set. Excellent correlation is found between the experimental and calculated spectra.

Contrast Media↗

Effects of separate and combined therapy with growth hormone and parathyroid hormone on lumbar vertebral bone in aged ovariectomized osteopenic rats.

Previous studies have demonstrated that growth hormone (GH) has a marked anabolic effect on cortical bone, and parathyroid hormone (PTH) has been shown to increase cancellous bone markedly and cortical bone to some extent in ovariectomized (ovx) rats. Combined therapies mostly focused on combining a bone anabolic agent with an antiresorptive agent. The following study was carried out to examine the efficacy of combined therapy with GH and PTH, two bone anabolic agents in rebuilding bone after loss due to ovariectomy in lumbar vertebrae, which contain both cortical and cancellous bones. Twelve-month-old female F344 rats were divided into five groups: sham + solvent vehicle, ovx + solvent vehicle, ovx + GH (2.5 mg/kg/day), ovx + PTH (80 microg/kg/day), and ovx + GH (2.5 mg/kg/day) + PTH (80 microg/kg/day). After surgery, animals were left for 4 months to become osteopenic before the beginning of therapy. Hormone administrations were given 5 days per week for 2 months and the animals were killed. The L3 vertebra was removed and examined by pQCT densitometry and by histomorphometry. Compared with age-matched, sham-operated controls, there was a 21% decrease in total bone mineral content (BMC) (p < 0.0001), 17.0% decrease in total bone mineral density (BMD) (p < 0.0001), 25.4% decrease in cortical BMC (p < 0.001), 3.1% decrease in cortical BMD (p < 0.05), 50.5% decrease in cancellous BMC (p < 0.01), 47.3% decrease in cancellous BMD (p < 0.01), and 14.5% decrease in cancellous bone volume (BV/TV) (p < 0.05) in the vehicle-treated ovx rats. Compared with age-matched, vehicle-treated ovx controls, GH, PTH, and GH + PTH increased total BMC by 22.8% (p < 0.001), 32.4% (p < 0.0001), and 72.7% (p < 0.0001), respectively; total BMD by 9.7% (p > 0.05), 22.6% (p < 0.001), and 38.8% (p < 0.0001), respectively; cortical BMC by 28.8% (p < 0.01), 50.8% (p < 0.0001), and 98.4% (p < 0.0001), respectively; and cortical BMD by 4.5% (p < 0.01), 2.9% (p < 0.05), and 6.3% (p < 0.0001), respectively. PTH and GH + PTH significantly increased cancellous BMC by 95.3% (p < 0.01) and 255.8% (p < 0.0001), respectively; cancellous BMD by 77.6% (p < 0.05) and 181% (p < 0.0001), respectively; cancellous BV/TV by 38.6% (p < 0.0001) and 55.9% (p < 0.0001), respectively; and trabecular thickness by 48% (p < 0.0001) and 68.3% (p < 0.0001), respectively. Note that GH by itself had no significant effect on vertebral cancellous BMC, cancellous BMD, and cancellous BV/TV. In conclusion, the effect of PTH was mostly more marked than that of GH. GH acted mainly by increasing cortical bone with less effect on cancellous bone, while PTH acted by increasing both cortical and cancellous bones. Combined therapy with GH and PTH was more effective in rebuilding bone after ovariectomy than either therapy alone. The effects of combined therapy with GH and PTH were additive in vertebral bone in the aged osteopenic rats.

Aging↗

Male rodent model of age-related bone loss in men.

Osteoporosis is a common occurrence in aging men. There is currently no appropriate animal model for studying age-related bone loss in men. To determine whether male Sprague-Dawley (SD) rats experience bone loss with aging and whether this rodent model is appropriate for studying age-related bone loss in men, SD rats aged 1-27 months were examined at the L-4 vertebra, the left femoral neck, and the left proximal tibia using peripheral quantitative computed tomography (pQCT) densitometry. In the L-4 vertebra of the male SD rats, cortical bone mineral content (BMC), cortical bone mineral density (BMD), and cortical bone thickness (Ct.Th) increased to a maximum at about 4 months of age and then plateaued. Vertebral cortical BMC began to decrease after about 13 months and vertebral Ct.Th began to decrease after about 9 months. By 27 months of age, vertebral cortical BMC decreased by 26.1% (p < 0.0001) and vertebral Ct.Th decreased by 31% (p < 0.0001). Vertebral cancellous BMC and vertebral cancellous BMD increased to a maximum at about 3 months of age and then declined progressively with aging after a short plateau. From 3 to 27 months of age, vertebral cancellous BMC and vertebral cancellous BMD had decreased linearly by 35.4% (p < 0.0001) and 49.4% (p < 0.0001), respectively. Both vertebral periosteal and vertebral endocortical perimeters of the L-4 vertebra of the rats increased with aging. From 9 to 27 months of age, the percent increase of vertebral endocortical perimeter (19.8%, p < 0.0001) was higher than that of vertebral periosteal perimeter (7.4%, p < 0.0001). This process was associated with a decrease with aging in vertebral Ct.Th. In addition, cancellous bone in the femoral neck and the proximal tibia began to be lost at 9 months of age and, by 27 months of age, cancellous BMC and cancellous BMD decreased by 59.7% (p < 0.0001) and 58.4% (p < 0.0001), respectively, in the femoral neck and by 72.2% (p < 0.0001) and 71.4% (p < 0.0001), respectively, in the proximal tibia. To gain further insight into the effects of aging on cancellous bone in the L-4 vertebra, histomorphometry was done on the L-4 vertebral body of animals aged 3, 6, 9, 18, and 24 months after pQCT densitometry. From 3 months of age and thereafter, cancellous bone volume (BV/TV) decreased progressively and, by 24 months, there was a decrease of 35.7% (p < 0.0001). In the L-4 vertebra, single- and double-labeled surfaces, mineral apposition rate (MAR), and bone formation rate (BFR/BS) decreased with aging. In conclusion, age-related bone loss in male SD rats started mostly from 9 months of age when bone growth had been completed. Aging male SD rats experience bone loss comparable to that seen in men. Thus, male SD rats represent an appropriate animal model of age-related bone loss in men. We recommend using male SD rats that are 9 months old as the starting age for age-related bone loss. We also suggest using the L-4 vertebra and femoral neck as the clinically relevant bone sites for determining the cause of the loss of bone, and how and whether therapeutic agents could modulate age-related bone loss in men.

Aging↗

Chemiluminescence investigation of detection of rutin in medicine and human urine using controlled-reagent-release technology.

A novel continuous-flow sensor based on chemiluminescence (CL) detection was developed for the determination of rutin in pharmaceutical preparations and human urine by controlled-reagent-release technology. The analytical reagents involved in the CL reaction, including luminol and hexacyanoferrate(III), were both immobilized on an anion-exchange column in a flow-injection system. The CL signal produced by the reaction between luminol and hexacyanoferrate(III), which were eluted from the column through sodium phosphate injection, was decreased in the presence of rutin. CL intensity was inhibited by rutin; the decrement of CL intensity was linear over the logarithm of the rutin concentration range of 1.0-400 ng x mL(-1), and the detection limit was 0.35 ng x mL(-1) (3 sigma). The whole process, including sampling and washing, could be completed in 1.5 min with a relative standard deviation of <3.5%. The flow sensor showed remarkable stability and could be easily reused >450 time; the sensor proposed was applied successfully to the determination of rutin in pharmaceutical preparations and human urine.

Chromatography, Ion Exchange↗

Does a diol cyclic urea inhibitor of HIV-1 protease bind tighter than its corresponding alcohol form? A study by free energy perturbation and continuum electrostatics calculations.

The cyclic urea inhibitors of HIV-1 protease generally have two hydroxyl groups on the seven-membered ring. In this study, free energy perturbation and continuum electrostatic calculations were used to study the contributions of the two hydroxyl groups to the binding affinity and solubility of a cyclic urea inhibitor DMP323. The results indicated that the inhibitor with one hydroxyl group has better binding affinity and solubility than the inhibitor with two hydroxyl groups. Therefore, removal of one hydroxyl group from DMP323 may help to improve the properties of DMP323. This is also likely to be true for other cyclic urea inhibitors. The study also illustrated the difficulty in accurate modeling of the binding affinities of HIV-1 protease inhibitors, which involves many possible protonation states of the two catalytic aspartic acids in the active site of the enzyme.

Azepines↗

Fatigue characteristics of ultra high molecular weight polyethylene with different molecular weight for implant material.

In order to investigate the effect of molecular weight on fatigue characteristics in the ultra high molecular weight polyethylene (UHMWPE), tension-tension fatigue tests of notched specimens were carried out in the present study. The effects of frequency and stress ratio on the fatigue characteristics were also investigated and fractography was discussed. The fatigue strength does not increase with increasing molecular weight. The fatigue strength might be influenced by the high degree of crystallinity in spite of the decreased tie molecule density in this study. Almost no effect of frequency on the number of cycles to failure can be observed. However, the higher the frequency, the higher the crack tip temperature. The effects of heat and strain rate on the fatigue strength must be considered in polymer materials. At a high stress ratio, the stress-number of cycles to failure (S-N) curves shift to high number cycles to failure side. Both stress amplitude and mean stress influence the fatigue life of UHMWPE.

Journal Article↗

Brain-derived neurotrophic factor (BDNF) is upregulated and associated with pain in chronic pancreatitis.

Our purpose was to investigate brain-derived neurotrophic factor (BDNF) in chronic pancreatitis (CP) in comparison with the normal pancreas and to evaluate its association with pain. By immunohistochemistry, in the normal pancreas BDNF immunoreactivity was moderately present in the cytoplasm of most ductal cells and weakly present in most acinar cells, islet cells, nerve fibers (including perineurium), and ganglia cells. In contrast, in CP intense immunostaining of BDNF was present in most cells of ductular complexes and in the perineurium of enlarged nerves. Moderate immunostaining of BDNF was found in degenerating acinar cells and islet cells. In addition, moderate immunoreactivity of BDNF was also detected in most enlarged nerve fibers and intrinsic pancreatic ganglia cells in CP samples. Western blot analysis also revealed 5.6-fold higher BDNF levels in CP samples (P < 0.01) compared with normal pancreas samples. The expression level of BDNF was positively correlated with pain intensity (P < 0.01) and pain frequency (P < 0.01) of CP patients. Furthermore, there was a significant relationship (r = 0.68, P < 0.01) between the BDNF immunostaining and the global pain scores. BDNF is increased in CP. Its association with pain suggests that it functions as a peripheral and central pain modulator, as reported previously in other inflammatory disorders.

Adolescent↗

Background light adaptation of the retinal neuronal adaptive system. I. Effect of background light intensity.

The behaviour of the neuronal adaptive retinal mechanisms to environmental light exposures was studied by measuring the oscillatory potentials (OPs) of the electroretinogram. Dark adapted rats were exposed to four levels of background light (BG), starting at a 'low scotopic' level of 1.43x 10(6) cd/m2, increased by steps of two log units, through 'high scotopic' -, 'low mesopic' - and finally the 'high mesopic' BG of 1.43x 10(0) cd/m2. The summed oscillatory response significantly increased as the BG intensity was raised, except at the 'high mesopic' level. The amplitudes of the a- and b-waves reduced as the BG light increased above the 'high scotopic' level. Each OP responded individually to the different BGs. O1 and O2, significantly enhanced at the 'low scotopic' BG. The amplitudes of the three later OPs increased significantly at the 'low mesopic' BG. The adaptational behaviour of the retinal oscillatory response to BG illumination was different to that of the a- and b- waves. The results indicate that the adaptational neuronal system, as reflected by the OPs, seems to be relatively robust and is separate from the slower photochemical adaptive process in the distal retina. The tentative corollary suggests the oscillatory system to play a vision-preserving role, possibly as an alert against undue depletion of the slowly regenerating visual pigment. The enhancement of the oscillatory response at the 'mesopic' illumination levels indicate both scotopic and photopic processes to contribute to neuronal adaptive activity of the retina.

Adaptation, Ocular↗