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Biomedical subjects

Yang Wang

Publications and source records attributed to Yang Wang.

At least 55 records · Page 3Linked to original sources

Hexa- and octacoordinate carbon in hydrocarbon cages: theoretical design and characterization.

A new series of hydrocarbon cages containing hexa- and octacoordinate carbon centers were designed theoretically by performing DFT calculations at the B3 LYP/6-311+G** level. Among these non-classical structures that were found to still obey the 8e rule, the two tetracations with octacoordinate carbons may be the first examples found in pure hydrocarbons. Structural characteristics, as well as thermodynamic and kinetic stabilities, were also investigated theoretically for these two octacoordinate tetracations. These hydrocarbon compounds containing hypercoordinate carbon centers provide a challenge for synthetic organic chemists.

Journal Article↗

Pivotal involvement of neurogenic mechanism in subcutaneous bee venom-induced inflammation and allodynia in unanesthetized conscious rats.

The bee venom (BV) model is a valid inflammatory pain model in animals and has been extended to human studies using its principle protein, mellitin. After subcutaneous (s.c.) injection of BV, long-lasting spontaneous nociception followed by thermal hyperalgesia, static allodynia, and local inflammatory response (edema) can be observed in rats. We hypothesize that (1) neurogenic components may contribute to the BV-induced inflammatory response and (2) static and dynamic mechanical allodynia may exist simultaneously in the BV model. Using different approaches including sciatic nerve transection (SCT), L4-L6 dorsal rhizotomy (DRT) and local treatment of the sciatic nerve with capsaicin, we found that SCT, DRT, and local capsaicin onto the sciatic nerve produced a significant inhibition of the BV-induced increase in volume of the injected paw, with a stronger effect of the SCT and the local capsaicin treatments than that of the DRT treatment. Static and dynamic mechanical allodynia in the BV test was assessed by measuring the paw withdrawal mechanical threshold and the paw withdrawal latency before and after the BV injection, respectively. Local capsaicin onto the sciatic nerve produced a significant inhibition of the BV-induced decrease in the paw withdrawal mechanical threshold, but not the paw withdrawal latency, of the injected paw. These findings suggest that neurogenic components, via dorsal root reflex and axon reflex mechanisms, are probably involved in the maintenance and the development of the BV-induced inflammation. In addition, the capsaicin-sensitive primary afferents may play differential roles in the development of the BV-induced static and dynamic mechanical allodynia.

Analysis of Variance↗

The role of Thr5 in human neuron growth inhibitory factor.

GIF, a member of the metallothionein (MT) family (assigned as MT3), is a neuron growth inhibitory factor that inhibits neuron outgrowth in Alzheimer's disease. The conserved Thr5 is one of the main differences between GIF and other members in the MT family. However, natural sheep GIF has an unusual Ala5, casting doubt on the role of common Thr5. We constructed a series of human GIF mutants at site 5, and characterized their biochemical properties by UV spectroscopy, circular dichroism spectroscopy, EDTA reaction, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) reaction, and pH titration. Their inhibitory activity toward neuron survival and neurite extension was also examined. Interestingly, the T5A mutant exhibited distinct metal thiolate activity in the EDTA and DTNB reactions, and also lost its bioactivity. Meanwhile, the T5S mutant had similar biochemical properties and biological activity as wild-type human GIF, indicating the hydroxyl group on the Thr5 was critical to the bioactivity of human GIF. We suggest the hydroxyl group in human GIF may help stabilize the biologically active conformation. On the other hand, lack of the hydroxyl group in sheep GIF may be partially compensated by its abnormal structure.

Animals↗

Gene expression, autonomic function and chronic hypoxia:lessons from the Andes.

Autonomic function is altered by altitude in sojourners and natives. We hypothesized that these physiologic responses are modulated by changes in gene expression. We compared gene product levels in 20 natives of Cerro de Pasco (CP), (4338 m), 10 of which had chronic mountain sickness (CMS) established by a CMS-scoring system, with gene products in the same men after 1 h at sea level. We further compared the results with those obtained from 10 US men residing at 1500 m. We measured gene products in white cells by reverse transcription polymerase chain reaction (RT-PCR). We focused on genes important in vascular autonomic physiology, and/or activated by hypoxia; hypoxia inducible factor 1-alpha (HIF 1-alpha), 2 splicing variants of vascular endothelial growth factor (VEGF); VEGF-121, VEGF-165, and phosphoglycerate kinase 1 (PGK 1). Normal CP natives showed high expression of all genes in CP, compared to US controls. Within 1 h of arrival at sea level, they had comparable levels to US residents. In CMS, the gene products were higher in CP. Although gene products decreased in Lima in this group, they never reached US values. VEGF 121 and 165 were correlated (P<0.001). VEGF 165 was higher in CMS in CP (P=0.006), and was positively correlated with CMS-score (R=0.86, P<0.001), and negatively correlated with arterial saturation (R=-0.79, P<0.001). Our findings underscore the changes in gene expression levels in intact humans in response to environmental stress. These changes may support the physiologic alterations induced by the ambient hypoxia at altitude and impact organism survival. They also suggest therapeutic strategies for autonomic and neurodegenerative diseases at sea level.

Adaptation, Physiological↗

[Long-term results of percutaneous sonographically-guided microwave ablation therapy of early-stage hepatocellular carcinoma].

OBJECTIVE: To evaluate the long-term results of percutaneous microwave coagulation therapy in the treatment of early hepatocellular carcinoma. METHODS: From May 1994 to June 2004, a total of 216 patients with 275 nodules of hepatocellular carcinoma whose diameter <or= 5 cm had undergone percutaneous microwave coagulation therapy (193 men, 23 women; mean age, 54.68 years). Institute review board approval and informed consent were obtained. Complete tumor necrosis rates, long-term survival rates, recurrence rates and the complications of the patients were analyzed. RESULTS: The mean follow-up period after microwave ablation was 40 months +/- 24 (range, 6 - 127 months). One hundred fifty-nine remained alive and consulted our hospital periodically as outpatients. Fifty-seven patients died. Complete tumor necrosis was seen in 95.64% (263/275) patients. One, 2, 3, 4 and 5-year cumulative survival rates were 94.87%, 88.81%, 80.44%, 74.97% and 68.63%, respectively. One, 2, 3, 4 and 5-year cumulative recurrence rates were 20.01%, 32.04%, 39.57%, 44.97% and 52.90%, respectively. Three patients have severe complications, including needle track implantation in one patient, biliary fistula in two patients. One patient died of pulmonary infection one week after the treatment. CONCLUSION: Sonographically-guided microwave coagulation therapy could make complete tumor necrosis in most cases of early hepatocellular carcinoma with low incidence of complications and this method has satisfactory long-term curative effect.

Adult↗

[Evaluation of long-term therapeutic effects of ultrasound-guided percutaneous microwave ablation of liver metastases].

OBJECTIVE: To explore therapeutic results of local microwave ablation for hepatic metastasis and the factors influencing the survival after percutaneous microwave ablation therapy. METHODS: From July 1995 to June 2005 128 patients with 282 hepatic metastases nodules with the primary diseases of upper gastrointestinal tumor (n = 26), colorectal tumor (n = 44), breast carcinoma (n = 19), pulmonary carcinoma (n = 15), and malignant tumor in other part of the body (n = 24), underwent percutaneous microwave ablation therapy and were followed up for 29.7 +/- 19.9 months (1 - 103 months). The largest diameter of the metastatic nodules was 3.5 +/- 1.6 cm (0.7 - 8.6 cm). Sixty-four cases had 140 nodules 3.0 cm in diameter. Forty-seven patients had single nodule, 44 patients had 2 nodules, and 93 patients had 3 or more nodules. Fifty-seven patients had tumor of low differentiation, 53 had tumor of middle differentiation, and 18 had highly differentiated tumors. Kaplan-Meier method was used to calculate the cumulative survival rate. Statistical comparison of the effects of potential predictive factors on survival rate was performed using log-rank analysis. Multivariate analysis of the survival rates was performed by using Cox's proportional hazard model. RESULTS: The 1, 2, 3, 4, and 5-year cumulative survival rates of all 128 patients were 90.88%, 73.84%, 51.09%, 36.14%, and 31.89% respectively. Univariate analysis showed that tumor size (P = 0.028), tumor differentiation (P = 0.026) and local recurrence or new metastases (P < 0.001) significantly affected the survival. Multivariate analysis revealed that tumor size (P = 0.035), recurrence or new metastases (P = 0.001) and tumor differentiation (P = 0.038) each had a significant effect on survival. CONCLUSION: There is a significantly higher probability of long-term survival for patients with well-differentiated tumors 3.0 cm or less in diameter and without recurrence or new metastasis after percutaneous microwave ablation.

Adult↗

The effect of D,L-beta-hydroxybutyric acid on cell death and proliferation in L929 cells.

As a prerequisite for tissue engineering applications, researchers must understand the effect on local cell types of the degradation products of biodegradable polymers. Polyhydroxybutyrate (PHB) has received special interest as an implant material, because it degrades to release a normal component of blood and tissue, D,L-beta-hydroxybutyrate (HB). We report that HB (0.02 g/l) promoted cell proliferation in cultured L929 cells plated at high cell density (1 x 10(5) cells/well) but not lower cell densities. While HB did not affect cell cycle progression, it significantly inhibited cell death. HB treatment prevented necrosis, reducing cell membrane permeability 4h following serum withdrawal from the medium, and for all subsequent time points. In summary, HB promotes proliferation of L929 cells in high-density cultures by preventing apoptotic and necrotic cell death. This property makes biodegradable polymers containing HB, such as PHBHHx, attractive candidates for tissue engineering applications, especially those requiring the regeneration of large numbers of cells.

3-Hydroxybutyric Acid↗

Quantitative measurement of cerebral haemodynamics in early vascular dementia and Alzheimer's disease.

Alzheimer's disease (AD) and vascular dementia (VaD) both share significant vascular risk factors. The present study measures the haemodynamics of these diseases in absolute rather than relative terms. Twenty-four patients were classified as either early AD or VaD and were compared with 12 non-cognitively impaired subjects. Magnetic resonance imaging flow quantification was used to measure arterial inflow and arterial pulse volume. Mean vascular resistance and compliance were calculated. In AD, the arterial inflow was lower by 18%, resistance was higher by 23% and compliance of the arterial tree was lower by 20% compared with normal (p=0.01, 0.02 and 0.05, respectively). In VaD, the arterial pulse volume was higher by 24% and compliance was higher by 35% compared with normal (p=0.05 for both). Early VaD is characterized by normal blood flow, but increased pulsation. Reduced blood flow and an incompliant arterial tree characterize early AD.

Aged↗

Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system.

The main purpose of this study was to prepare lipid-based self-microemulsifying drug delivery system (SMEDDS) to improve peroral bioavailability of silymarin. SMEDDS was a system consisting of silymarin, Tween 80, ethyl alcohol, and ethyl linoleate. Particle size change of the microemulsion was evaluated upon dilution with aqueous media and loading with incremental amount of silymarin. In vitro release was investigated by a dialysis or an ultrafiltration method. Results showed that release of silymarin from SMEDDS was limited, incomplete, and typical of sustained characteristics. Pharmacokinetics and bioavailability of silymarin suspension, solution, and SMEDDS were evaluated and compared in rabbits. Plasma silybin, which was treated as the representing component of silymarin, was determined by high-performance liquid chromatography. After gavage administration of silymarin suspension, plasma silybin level was very low and fell below limit of detection 4h after. As for silymarin solution and SMEDDS, double peak of maximum concentrations were observed, which was characteristic of enterohepatic circulation. Relative bioavailability of SMEDDS was dramatically enhanced in an average of 1.88- and 48.82-fold that of silymarin PEG 400 solution and suspension, respectively. It was concluded that bioavailability of silymarin was enhanced greatly by SMEDDS. Alternative mechanisms, such as improved lymphatic transport pathway, other than improved release may contribute to enhancement of bioavailability of silymarin.

Animals↗

[The effect of combination of glycine and methylprednisolone on Kupffer cells of liver after hemorrhagic shock in rats].

OBJECTIVE: To investigate the effect of combination of glycine and methylprednisolone (MP) on Kupffer cells in liver of rats suffered from hemorrhagic shock. METHODS: Fifty Wistar rats were bled to establish the shock model and subsequently resuscitated with shed blood and normal saline. Just prior to resuscitation, the rats were randomly assigned to 5 groups: sham group, shock group, shock + glycine group, shock + MP group and shock + glycine + MP group. The intracellular calcium concentration and the level of tumor necrosis factor alpha (TNF alpha) in the culture medium of Kupffer cells were determined after stimulation with different concentrations (1, 10, 100 and 1000 ng/ml) of lipopolysaccharide (LPS). RESULTS: Concentration of intracellular calcium and production of TNF-alpha by isolated Kupffer cells stimulated by LPS were elevated significantly in the rats with hemorrhagic shock, which were totally prevented by glycine + MP compared with other groups (P < 0.005). CONCLUSIONS: The combination of glycine and MP prevents the increase of intracellular calcium of Kupffer cell, suppress Kupffer cell activation, decrease the production of TNF-alpha of Kupffer cell and block systemic inflammatory responses more effectively than single administer of glycine or MP.

Animals↗

[Repair of skin damage with mesenchymal stem cells-poly (lactic-co-glycolic acid) scaffolds: experimental study with rabbits].

OBJECTIVE: To evaluate the feasibility and effect of mesenchymal stem cells (MSCs)-poly (lactic-co-glycolic acid) (PLGA) scaffold as transplant in repair of skin damage. METHODS: MSCs were isolated from the bone marrow of femur of a one-month-old New Zealand rabbit, cultured, and labeled with diamidino-phenyl-indole (DAPI). Porous foam scaffolds were made with PLGA. MSCs of 2 - 3 passages were seeded on the scaffolds. Fluorescence microscopy and scanning electron microscopy were used to observe the growth of the MSCs. Six pieces of skin 2 cm x 2 cm in size were cut from the backs of five 5-month-old new Zealand rabbits and then 4 pieces of MSCs- PLGA scaffolds and 2 pieces of porous foam PLGA scaffolds of the size similar to these of the cut skin were transplanted to the skin wounds. The wound healing was observed. Five days after the operation, samples of newly-grown skin were taken to undergo HE staining, VG staining, and microscopy. Immunofluorescence histochemistry was used to detect the cytokeratin AE1/AE3. RESULTS: Scanning electron microscopy showed that holes were distributed evenly on the surface of and inside the porous foam PLGA scaffolds Fluorescence microscopy and scanning electron microscopy showed that the MSCs grew well on the porous foam PLGA scaffolds and the number of MSCs increased gradually. Animal experiment showed that with the degradation of the polymer scaffolds the wounds were gradually covered by newly grown skin similar to the normal skin. Immunofluorescence histochemistry showed fluorescence positive cells in the stratum corneum and follicles. The wounds transplanted only with porous foam PLGA scaffolds formed new skin too, however, in the dermis of the new skin only thickened fibrous scars and a few follicles were seen. CONCLUSION: The compound of MSCs-PLGA polymer is effective in wound healing.

Animals↗

N-thiolated beta-lactams: a new family of anti-Bacillus agents.

This report describes the evaluation of N-thiolated beta-lactam antibiotics as potential anti-Bacillus agents. N-Thiolated beta-lactams are a new family of antibacterials that previously have been found to selectively inhibit the growth of Staphylococcus bacteria over many other genera of microbes. From the data presented herein, these lactams similarly inhibit a variety of Bacillus species, including Bacillus anthracis. The preliminary structure-activity studies suggest that there is a need to balance the lipophilic character of the C3/C4 groups in order to obtain optimal anti-Bacillus activity. Elongation or extensive branching of the organothio substituent diminishes antibacterial effects, with the sec-butylthio derivative providing the strongest activity.

Anti-Bacterial Agents↗

Novel polymeric prodrug with multivalent components for cancer therapy.

We designed, synthesized, and evaluated in vitro and in vivo a novel targeted anticancer polymeric prodrug containing multiple copies of tumor targeting moiety [synthetic luteinizing hormone-releasing hormone (LHRH) peptide, analog of LHRH] and anticancer drug (camptothecin). One, two, or three molecules of the targeting peptide and anticancer drug were covalently conjugated with bis(2-carboxyethyl) polyethylene glycol polymer using citric acid as a multivalent spacer. We showed that LHRH peptide was bound to extracellular receptors and localized in plasma membrane of cancer cells. The designed tumor-targeted prodrug increased the solubility of anticancer drug and offered cytoplasmic and/or nuclear delivery of drug to cancer cells expressing LHRH receptors. The multicomponent prodrug containing three copies of the targeting peptide and drug was almost 100 times more cytotoxic and substantially had enhanced antitumor activity compared with the analogous nontargeted prodrug and prodrugs containing one or two copies of active components.

Animals↗

Interaction of beta-1,3-glucan with its recognition protein activates hemolymph proteinase 14, an initiation enzyme of the prophenoloxidase activation system in Manduca sexta.

A serine proteinase pathway in insect hemolymph leads to prophenoloxidase activation, an innate immune response against pathogen infection. In the tobacco hornworm Manduca sexta, recombinant hemolymph proteinase 14 precursor (pro-HP14) interacts with peptidoglycan, autoactivates, and initiates the proteinase cascade (Ji, C., Wang, Y., Guo, X., Hartson, S., and Jiang, H. (2004) J. Biol. Chem. 279, 34101-34106). Here, we report the purification and characterization of pro-HP14 from the hemolymph of bacteria-injected M. sexta larvae. The zymogen, consisting of a single polypeptide with a molecular mass of 68.5 kDa, is truncated at the amino terminus. It is converted to a two-chain active form in the presence of beta-1,3-glucan (a fungal cell wall component) and beta-1,3-glucan recognition protein-2. The 45-kDa heavy chain contains four low-density lipoprotein receptor A repeats, one Sushi domain, and one unique cysteine-rich region, whereas the 30-kDa light chain contains a serine proteinase domain, which was labeled by [(3)H]diisopropyl fluorophosphate. Pro-HP14 in the plasma strongly binds curdlan, zymosan, and yeast and interacts with peptidoglycan and Micrococcus luteus. Addition of autoactivated HP14 elevated phenoloxidase activity level in the larval plasma. Recombinant M. sexta serpin-1I reduced prophenoloxidase activation by inhibiting HP14. These data are consistent with the current model on initiation and regulation of the prophenoloxidase activation cascade upon recognition of pathogen-associated molecular patterns by specific pattern recognition proteins.

Animals↗

Identification of a novel C2 domain factor in ovaries of orange-spotted grouper (Epinephelus coioides).

Follicle consists of an oocyte and a lot of surrounding follicular cells, and significant interactions exist between the oocyte and the somatic cells. In this study, a novel cDNA has been screened from a subtractive cDNA library between tail bud embryos and blastula embryos in the protogynous hermaphrodite orange-spotted grouper (Epinephelus coioides). Its full-length cDNA is 821 bp, and has an ORF of 414 bp for encoding a peptide of 137 aa, which shows 38%, 37%, 33%, and 33% homology with 4 putative proteins screened from zebrafish (Danio rerio). Conserved domain search in NCBI reveals a single C2 domain existing in the C2 domain superfamily proteins, and has only 7 beta strands in comparison with 8 beta strands of C2 domains in other C2 domain superfamily proteins. Artificial sex reversal, RT-PCR analysis and Western blot detection demonstrated ovary-specific expression of the C2 domain factor, and therefore the novel gene was designated as E. coioides ovary-specific C2 domain factor, EcOC2 factor. Moreover, predominant expression of EcOC2 factor was further revealed in grouper mature ovary, and its strong immunofluorescence signals were located between granulosa cells and oocyte zona radiata in grouper mature follicles. The data indicate that the novel EcOC2 factor might be a main component that associates between granulosa cells and the oocyte during oocyte maturation, and might play significant roles in regulating oocyte maturation and ovulation. Further studies on its developmental behaviour and physiological functions will elucidate the interactions between oocyte and the surrounding somatic cells and the underlying molecular mechanisms.

Amino Acid Sequence↗

Novel distance-based atom-type topological indices DAI for QSPR/QSAR studies of alcohols.

In this work, we propose a distance-based atom-type topological index (DAI) for quantitative structure-property/activity relationship (QSPR/QSAR) studies. The newly constructed index, which codes the structural environment of each atom type in a molecule, can be calculated simply. These atom-type topological indices, along with our recently proposed Lu index, were used to construct QSPR/QSAR models for several representative physical properties and biological activities of several data sets of alcohols with a range of non-hydrogen atoms by using multiple linear regression (MLR) analysis. The efficiency of these indices is verified by high quality QSPR models. The results indicate that the combined use of Lu and DAI indices promises to be a useful method for QSPR/QSAR analysis of complex compounds.

Alcohols↗

Dual-echo spiral in/in acquisition method for reducing magnetic susceptibility artifacts in blood-oxygen-level-dependent functional magnetic resonance imaging.

MRI signal dropout in gradient recalled echo acquisitions limits the capability of blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) to study activation tasks that involve the orbitofrontal, temporal, and basal areas of the brain where significant macroscopic magnetic susceptibility differences exist. Among the various approaches aimed to address this issue, the acquisition method based on spiral in/out trajectories is one of the most time-efficient and effective techniques. In this study, we extended further the spiral in/out approach into 3D acquisition and compared the effectiveness of the different spiral in/out trajectory combinations in reducing signal dropout. The activation results from whole brain fMRI studies using complex finger tapping and breath-holding tasks demonstrate that the acquisition method based on dual-echo spiral in/in (DSPIN) trajectories is the most favorable. The DSPIN acquisition method has the following advantages: (1) It reduces most effectively signal dropout in the brain where magnetic susceptibility inhomogeneity is problematic and significantly improves the sensitivity to detect functional activations in those regions. (2) It significantly improves SNR in the whole brain by dual echo averaging without compromising functional contrast. (3) There is no reduction in time-efficiency and spatial resolution.

Adult↗