Biomedical subjects

Yadong Wang

Publications and source records attributed to Yadong Wang.

15 recordsLinked to original sources

PubMed2026

The application of the CRISPR-Cas system in Pseudomonas aeruginosa infections.

Due to the extensive drug resistance of Pseudomonas aeruginosa (P. aeruginosa), it is still a great clinical challenge. The clustered regularly interspaced short palindromic repeats and associated proteins (CRISPR-Cas) system has become a promising strategy against this pathogen. This review critically evaluates the multifaceted applications of CRISPR-Cas technology in P. aeruginosa, including its role in antimicrobial resistance, diagnostics, genome editing, and emerging therapeutic and vaccine strategies. In addition to conducting a comprehensive analysis of various studies, we also compared the performance and limitations of various CRISPR platforms, and discussed the main technologies and transformation obstacles in this field. Finally, we look forward to the direction of applying these experimental tools to clinical research in the future.

Pseudomonas aeruginosa↗

PubMed2006

A neuroinductive biomaterial based on dopamine.

Chemical messengers such as neurotransmitters play an important role in cell communication, differentiation, and survival. We have designed and synthesized a bioactive biomaterial that derived its biological activity from dopamine. The resultant biodegradable polymer, PCD, has pendent groups bearing dopamine functionalities. Image analysis demonstrated that nerve growth factor-primed rat pheochromocytoma cells (PC12) and explanted rat dorsal root ganglions attached well and displayed substantial neurite outgrowth on the polymer surface. Furthermore, PCD promoted more vigorous neurite outgrowth in PC12 cells than tissue culture polystyrene, laminin, and poly(d-lysine). The histogram of neurite length of PC12 cells showed distinctive patterns on PCD that were absent on the controls. A subset of PC12 cells displayed high filopodium density on PCD. The addition of dopamine in culture medium had little effect on the differentiation of PC12 cells on tissue culture polystyrene. Tyrosine, the precursor of dopamine, did not exhibit this ability to impart specific bioactivity to an analogous polymer. Thus, the dopamine functional group is likely the origin of the inductive effect. PCD did not cause nerve degeneration or fibrous encapsulation when implanted immediately adjacent to the rat sciatic nerves. This work is a step toward creating a diverse family of bioactive materials using small chemical messengers as monomers.

Animals↗

PubMed2006

High-density arrays of InGaN nanorings, nanodots, and nanoarrows fabricated by a template-assisted approach.

Dense, crystalline arrays of InGaN nanorings, nanodots, and nanoarrows have been fabricated on GaN substrates by template-assisted nano-area selective growth. To create the nanostructures, we have used nanoporous anodic alumina films as templates to pattern nanopores in an SiO2 transfer layer, and then used this patterned SiO2 layer as a template for nitride growth by metalorganic chemical vapor deposition. We have varied the diameter of the deposited nitride nanostructures from 35 to 250 nm by changing the initial anodic alumina template structure. In addition, by controlling the nitride growth time we have created various types of nanostructures, from nanorings to nanoarrows. This structural evolution begins with the nucleation and formation of a nanoring structure, followed by coalescence and growth to form faceted nanodots, and finally lateral overgrowth to form faceted nanoarrows.

Journal Article↗

PubMed2006

Concurrent encoding of frequency and amplitude modulation in human auditory cortex: MEG evidence.

A natural sound can be described by dynamic changes in envelope (amplitude) and carrier (frequency), corresponding to amplitude modulation (AM) and frequency modulation (FM), respectively. Although the neural responses to both AM and FM sounds are extensively studied in both animals and humans, it is uncertain how they are corepresented when changed simultaneously but independently, as is typical for ecologically natural signals. This study elucidates the neural coding of such sounds in human auditory cortex using magnetoencephalography (MEG). Using stimuli with both sinusoidal modulated envelope (f(AM), 37 Hz) and carrier frequency (f(FM), 0.3-8 Hz), it is demonstrated that AM and FM stimulus dynamics are corepresented in the neural code of human auditory cortex. The stimulus AM dynamics are represented neurally with AM encoding, by the auditory steady-state response (aSSR) at f(AM). For sounds with slowly changing carrier frequency (f(FM) <5 Hz), it is shown that the stimulus FM dynamics are tracked by the phase of the aSSR, demonstrating neural phase modulation (PM) encoding of the stimulus carrier frequency. For sounds with faster carrier frequency change (f(FM) > or = 5 Hz), it is shown that modulation encoding of stimulus FM dynamics persists, but the neural encoding is no longer purely PM. This result is consistent with the recruitment of additional neural AM encoding over and above the original neural PM encoding, indicating that both the amplitude and phase of the aSSR at f(AM) track the stimulus FM dynamics. A neural model is suggested to account for these observations.

Acoustic Stimulation↗

PubMed2006

Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds.

We report that the functional assembly of engineered cardiac muscle can be enhanced by oxygen supply provided by mechanisms resembling those in normal vascularized tissues. To mimic the capillary network, cardiomyocytes and fibroblasts isolated from the neonatal rat hearts were cultured on a highly porous elastomer with a parallel array of channels that were perfused with culture medium. To mimic oxygen supply by hemoglobin, culture medium was supplemented with a perfluorocarbon (PFC) emulsion; constructs perfused with unsupplemented culture medium served as controls. In PFC-supplemented medium, the decrease in the partial pressure of oxygen in the aqueous phase was only 50% of that in control medium (28 mmHg vs. 45 mmHg between the construct inlet and outlet at a flow rate of 0.1 mL/min). Consistently, constructs cultivated in the presence of PFC contained higher amounts of DNA and cardiac markers (troponin I, connexin-43) and had significantly better contractile properties as compared to control constructs. In both groups, electron microscopy revealed open channels and the presence of cells at the channel surfaces as well as within constructs. Improved properties of cardiac constructs could be correlated with the enhanced supply of oxygen to the cells, by a combined use of channeled scaffolds and PFC.

Animals↗

PubMed2006

Macroporous elastomeric scaffolds with extensive micropores for soft tissue engineering.

Macroporous scaffolds are of great value in tissue engineering. We have developed a method to fabricate macroporous scaffolds from a biocompatible and biodegradable elastomer, poly(glycerol sebacate) (PGS). This method is potentially very useful for soft tissue engineering. Our fabrication method produced macroporous scaffolds with extensive micropores. We fabricated flat scaffolds and tubular scaffolds of uniform thickness. This fabrication method demonstrated good control of variables such as pore size, porosity, and pore interconnectivity. Sodium chloride (salt) crystals, which served as solid porogens, were packed into a mold and fused in a humid chamber. PGS was cured while dispersed throughout the fused salt template. Dissolution of the salt and subsequent lyophilization produced elastomer sponges with approximately 90% porosity, interconnected macropores (75-150 microm), and extensive micropores (5-20 microm). The macropores were generated by the salt particles, while the micropores were likely generated by glycerol vapor formed during PGS curing. Such numerous micropores could facilitate cell-cell interactions and mass transport. Fibroblasts adhered to and proliferated well within the PGS scaffolds and formed three-dimensional tissue-engineered constructs within 8 days.

Animals↗

PubMed2006

Real time decomposition of speech into modulated components.

Motivated by the active process of the outer hair cell (OHC) in the mammalian inner ear, a real time decomposition of speech into modulated components is presented. A generalized phase lock loop (GPLL) was applied to decompose the speech signal into its envelope and positive instantaneous frequency (PIF) parts, which can be further processed and represented by timing information alone. A log-derivative operator is applied to the bandpass signal. Analytic and antianalytic components occupying non overlapping frequency bands are separated by filtering. The proposed algorithms are used to represent speech signals processed through a bandpass filter bank.

Acoustic Stimulation↗

PubMed2005

Combined tumor therapy by using radiofrequency ablation and 5-FU-laden polymer implants: evaluation in rats and rabbits.

PURPOSE: To evaluate the use of 5-fluorouracil (5-FU)-laden polymer implants as an adjunct to radiofrequency (RF) ablation for tumor treatment. MATERIALS AND METHODS: All animal studies were performed in compliance with the Case Western Reserve University Institutional Animal Care and Use Committee guidelines. Three studies were performed to investigate (a) in vitro dissolution of 5-FU-laden polymer implants in saline and bovine serum, (b) tissue distribution of 5-FU and its metabolite, 5-fluorouridine (5-FUrd), in the ablated liver tissue of rats (n = 4), and (c) efficacy of combined approach (n = 4) compared with that of ablation alone (n = 6) for VX2 liver tumor model in rabbits. Characterization of 5-FU release in vitro and distribution of 5-FU in rat liver tissue were analyzed by using high performance liquid chromatography; in vivo efficacy was assessed by using computed tomography and pathologic examination. RESULTS: Results of the in vitro dissolution study showed that a 75% release of 5-FU occurred in 2 days when exposed to bovine serum and in 9 days when exposed to phosphate-buffered saline. In the ablated rat liver, the 5-FU level was higher at the center and lower at the periphery of the tissue both at 24 hours (41.0 mg per kilogram tissue vs 15.0 mg per kilogram tissue, respectively) and at 48 hours (8.0 mg per kilogram tissue vs 2.0 mg per kilogram tissue, respectively). The 5-FUrd concentration was twofold higher peripherally than centrally and was higher at 48 hours than at 24 hours. In rabbits, local delivery of 5-FU immediately after RF ablation provided a significant (P < .05) reduction in tumor size compared with ablation alone (1.80 cm3 +/- 0.28 [standard error] vs 3.53 cm3 +/- 0.52, respectively; P = .034) and a more than 20-fold reduction in tumor size compared with the control (1.80 cm3 +/- 0.28 vs 41.95 cm3 +/- 11.58, respectively; P = .018). CONCLUSION: Combined treatment by using 5-FU polymer implants and RF ablation shows uniform sustained release of 5-FU for 48 hours at least 8 mm from the edge of the ablation zone and appears to be successful at controlling the growth of an experimental tumor in rabbits appreciably better than does ablation alone.

Animals↗

PubMed2005

Fully complex magnetoencephalography.

Complex numbers appear naturally in biology whenever a system can be analyzed in the frequency domain, such as physiological data from magnetoencephalography (MEG). For example, the MEG steady state response to a modulated auditory stimulus generates a complex magnetic field for each MEG channel, equal to the Fourier transform at the stimulus modulation frequency. The complex nature of these data sets, often not taken advantage of, is fully exploited here with new methods. Whole-head, complex magnetic data can be used to estimate complex neural current sources, and standard methods of source estimation naturally generalize for complex sources. We show that a general complex neural vector source is described by its location, magnitude, and direction, but also by a phase and by an additional perpendicular component. We give natural interpretations of all the parameters for the complex equivalent-current dipole by linking them to the underlying neurophysiology. We demonstrate complex magnetic fields, and their equivalent fully complex current sources, with both simulations and experimental data.

Algorithms↗

PubMed2005

Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material.

No satisfactory method currently exists for bridging neural defects. Autografts lead to inadequate functional recovery, and most available artificial neural conduits possess unfavorable swelling and pro-inflammatory characteristics. This study examined the biocompatibility of a novel biodegradable elastomer, poly(glycerol sebacate) (PGS), for neural reconstruction applications, as the material possesses favorable mechanical property and degradation characteristics. The effect of PGS on Schwann cell metabolic activity, attachment, proliferation, and apoptosis were examined in vitro in comparison with poly(lactide-co-glycolide) (PLGA), a biomaterial widely utilized for tissue engineering applications. The in vivo tissue response to PGS was compared with PLGA implanted juxtaposed to the sciatic nerve; the physical changes in the implant material were measured during the degradation process. PGS had no deleterious effect on Schwann cell metabolic activity, attachment, or proliferation, and did not induce apoptosis; the in vitro effects of PGS were similar to or superior to that of PLGA. In vivo, PGS demonstrated a favorable tissue response profile compared with PLGA, with significantly less inflammation and fibrosis and without detectable swelling during degradation. PGS is an excellent candidate material for neural reconstruction applications given its lack of in vitro Schwann cell toxicity and minimal in vivo tissue response.

Animals↗

PubMed2004

Gene mining: a novel and powerful ensemble decision approach to hunting for disease genes using microarray expression profiling.

Current applications of microarrays focus on precise classification or discovery of biological types, for example tumor versus normal phenotypes in cancer research. Several challenging scientific tasks in the post-genomic epoch, like hunting for the genes underlying complex diseases from genome-wide gene expression profiles and thereby building the corresponding gene networks, are largely overlooked because of the lack of an efficient analysis approach. We have thus developed an innovative ensemble decision approach, which can efficiently perform multiple gene mining tasks. An application of this approach to analyze two publicly available data sets (colon data and leukemia data) identified 20 highly significant colon cancer genes and 23 highly significant molecular signatures for refining the acute leukemia phenotype, most of which have been verified either by biological experiments or by alternative analysis approaches. Furthermore, the globally optimal gene subsets identified by the novel approach have so far achieved the highest accuracy for classification of colon cancer tissue types. Establishment of this analysis strategy has offered the promise of advancing microarray technology as a means of deciphering the involved genetic complexities of complex diseases.

Acute Disease↗

PubMed2003

In vivo degradation characteristics of poly(glycerol sebacate).

We have developed a series of biodegradable elastomers, poly(glycerol sebacate) (PGS), based on glycerol and sebacic acid. The polymers are potentially useful in soft tissue regeneration and engineering. To evaluate the performance of PGS in a physiological environment, we compared their degradation profiles with poly(DL-lactide-co-glycolide) (50:50, carboxyl ended, M(w) 15,000) in vivo. Among the parameters examined are changes in weight and mechanical strength with time, implant geometry, surface characteristics, and degree of swelling. Unlike poly(DL-lactide-co-glycolide), PGS primarily degrades by surface erosion, which gives a linear degradation profile of mass, preservation of geometry and intact surface, and retention of mechanical strength.

Absorbable Implants↗

PubMed2002

A tough biodegradable elastomer.

Biodegradable polymers have significant potential in biotechnology and bioengineering. However, for some applications, they are limited by their inferior mechanical properties and unsatisfactory compatibility with cells and tissues. A strong, biodegradable, and biocompatible elastomer could be useful for fields such as tissue engineering, drug delivery, and in vivo sensing. We designed, synthesized, and characterized a tough biodegradable elastomer from biocompatible monomers. This elastomer forms a covalently crosslinked, three-dimensional network of random coils with hydroxyl groups attached to its backbone. Both crosslinking and the hydrogen-bonding interactions between the hydroxyl groups likely contribute to the unique properties of the elastomer. In vitro and in vivo studies show that the polymer has good biocompatibility. Polymer implants under animal skin are absorbed completely within 60 days with restoration of the implantation sites to their normal architecture.

3T3 Cells↗

PubMedDate not supplied

Toward a carbohydrate-based HIV-1 vaccine: synthesis and immunological studies of oligomannose-containing glycoconjugates.

Human antibody 2G12 is a broadly neutralizing antibody that exerts its anti-HIV activity by targeting a novel oligomannose cluster on HIV-1 gp120. It was previously demonstrated that synthetic oligomannose clusters could mimic the carbohydrate epitope of 2G12 and showed enhanced antigenicity (Wang L. X. et al. (2004) Chem.Biol. 11, 127). This paper describes the synthesis of oligomannose-containing glycoconjugates that include either a carrier protein or a universal T-helper epitope peptide to provide an effective immunogen. It was shown that the synthetic neoglycoconjugates containing oligomannose clusters could be recognized by the human antibody 2G12. Rabbit immunization studies revealed that only a small fraction of antibodies raised by the glycoconjugates was directed to the carbohydrate antigens, with the majority of the IgG type antibodies being directed to the linkers in the conjugates. The anti-sera showed weak cross-reactivity to HIV-1 gp120.

AIDS Vaccines↗

PubMedDate not supplied

Endothelialized microvasculature based on a biodegradable elastomer.

Vital organs maintain dense microvasculature to sustain the proper function of their cells. For tissue- engineered organs to function properly, artificial capillary networks must be developed. We have microfabricated capillary networks with a biodegradable and biocompatible elastomer, poly(glycerol sebacate) (PGS). We etched capillary patterns onto silicon wafers by standard micro-electromechanical systems (MEMS) techniques. The resultant silicon wafers served as micromolds for the devices. We bond the patterned PGS film with a flat film to create capillary networks that were perfused with a syringe pump at a physiological flow rate. The devices were endothelialized under flow conditions, and part of the lumens reached confluence within 14 days of culture. This approach may lead to tissue-engineered microvasculature that is critical in vital organs engineering.

Biocompatible Materials↗