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Biomedical subjects

Yang Liu

Publications and source records attributed to Yang Liu.

At least 163 records · Page 9Linked to original sources

FoxP3: a genetic link between immunodeficiency and autoimmune diseases.

It has long been observed that patients with autoimmune diseases also have immune deficiency. How these two opposite extremes of immunity can be found in the same individual is largely unclear. Here we review the evidence that a FoxP3 defect may provide a critical link between autoimmunity and immune deficiency. Disruption of FoxP3 results in severe autoimmune syndromes in both human and mice. Bone marrow chimera experiments indicate that FoxP3 defects in both hematopoietic and non-hematopoietic cells are required for the development of severe autoimmune disease. FoxP3 mutation in the hematopoietic cells impairs the development of regulatory T cells (Treg). Our data demonstrate that the mutation in non-hematopoietic cells results in deficient thymopoiesis. Defective T cell production may be an underlying cause of T cell hyperproliferation, which together with Treg defects, may lead to fatal autoimmune disease in mouse and man.

Animals↗

Effect of hexanol on the reversed micelles of Span 85 modified with Cibacron Blue F-3GA for protein solubilization.

Sorbitan trioleate (Span 85) modified with Cibacron Blue F-3GA (CB) was used as an affinity surfactant (CB-Span 85) to form affinity-based reversed micelles in n-hexane. It was found that the addition of hexanol to the reversed micellar system resulted in a significant increase in water content and hydrodynamic radius of the affinity-based reversed micelles. Moreover, the reversed micelles with hexanol revealed broader aggregation number distribution and larger average aggregation number than the reversed micelles without hexanol addition. This is considered to be due to the decreases in the micellar curvature and rigidity of the micellar interfacial layer and the increase in the micellar interfacial fluidity. Consequently, the solubilization capacity of lysozyme increased about 70% in the reversed micellar solution with 3 vol% hexanol. On the other hand, the capacity of BSA was only 30% increased under the same conditions due to its larger molecular size than lysozyme. Kinetic analysis revealed that the increase in the micellar interfacial fluidity in the presence of hexanol resulted in faster release of lysozyme from the micelles, thus leading to an increase of the overall volumetric mass transfer coefficient in the back extraction.

Hexanols↗

Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells.

If irradiated tumor cells could be rendered immunogenic, they would provide a safe, broad, and patient-specific array of antigens for immunotherapies. Prior approaches have emphasized genetic transduction of live tumor cells to express cytokines, costimulators, and surrogate foreign antigens. We asked if immunity could be achieved by delivering irradiated, major histocompatibility complex-negative plasmacytoma cells to maturing mouse dendritic cells (DCs) within lymphoid organs. Tumor cells injected intravenously (i.v.) were captured by splenic DCs, whereas subcutaneous (s.c.) injection led only to weak uptake in lymph node or spleen. The natural killer T (NKT) cells mobilizing glycolipid alpha-galactosyl ceramide, used to mature splenic DCs, served as an effective adjuvant to induce protective immunity. This adjuvant function was mimicked by a combination of poly IC and agonistic alphaCD40 antibody. The adjuvant glycolipid had to be coadministered with tumor cells i.v. rather than s.c. Specific resistance was generated both to a plasmacytoma and lymphoma. The resistance afforded by a single vaccination lasted >2 mo and required both CD4+ and CD8+ T cells. Mature tumor capturing DCs stimulated the differentiation of P1A tumor antigen-specific, CD8+ T cells and uniquely transferred tumor resistance to naive mice. Therefore, the access of dying tumor cells to DCs that are maturing to activated NKT cells efficiently induces long-lived adaptive resistance.

Adjuvants, Immunologic↗

Morphology-controlled synthesis of monodisperse ZnO troughs at the air-water interface under mild conditions.

In this work, an interfacial synthetic strategy to produce ZnO troughs at the air-water interface under mild conditions was demonstrated. The as-prepared ZnO trough was monodisperse, single crystalline, and pure. By manipulation of the magnet stirring time, the fabricated ZnO can be manipulated as an independent or intertwined trough. Various preparative parameters, such as initial reactants and their concentrations, had been examined, and the results revealed that troughlike ZnO could be only obtained by adopting zinc acetate and hexamethylenetetramine as precursors at concentrations larger than 0.01 M. The as-obtained ZnO, within the dimension of several micrometers, showed a trough-related photoluminescence emission at 356 nm. Moreover, the evolution process of a ZnO trough after reaction for 5, 30, 60, and 90 min was viewed by X-ray diffraction and field emission scanning electron microscopy characterization, and a possible mechanism was also proposed and discussed, which might help us to further our understanding toward the reaction mechanism at the air-water interface.

Air↗

Monomers for preparation of amide-linked RNA: asymmetric synthesis of all four nucleoside 5'-azido 3'-carboxylic acids.

[reaction: see text] Recent discovery of RNA interference as an efficient and naturally occurring mechanism of gene regulation has reinvigorated the interest in chemically modified RNA. For potential in-vivo applications small interfering RNAs require chemical modifications to fine-tune the thermal stability and increase the cellular delivery and potency and in vivo half-life of the RNA duplexes. From this perspective, amides as neutral and hydrophobic internucleoside linkages in RNA are highly interesting modifications for RNA interference. Amides are remarkably good mimics of the phosphodiester backbone of RNA and can be prepared using a relatively straightforward peptide coupling chemistry. However, the progress in the field has been hampered by the shortage of efficient methods to synthesize the monomeric building blocks for such couplings, the nucleoside amino acid equivalents. Herein, we report enantioselective synthesis of 5'-azido 3'-carboxylic acid derivatives of all four natural ribonucleosides. The key transformations in our synthesis are a double asymmetric ene reaction and a stereoselective iodolactonization that form the basic carbon skeleton of the modified ribose. Standard nucleoside synthesis is followed by a short and highly efficient protecting group manipulation to give the enantiomerically pure (>98%) title compounds in 9-10 steps and 15-19% overall yields starting from small achiral molecules. The present results are a significant improvement over our first-generation racemic synthesis and compare favorably with the previously reported synthesis from nucleoside and carbohydrate precursors.

Amides↗

Fabrication and characterizations of oligopyrrole doped with dodecylbenzenesulfonic acid in reverse microemulsion.

The pyrrole-oligomer nanoparticles doped dodecylbenzenesulfonic acid (DBSA) have been fabricated in water-DBSA-isopropyl alcohol-isooctane reverse microemulsion, since DBSA could play the roles of both surfactant and dopant. We have found the optimum synthetic conditions by the analysis of factors affecting the yield and conductivity of oligopyrrole. The effect of solubility on the improved properties of DBSA-oligopyrrole in some organic solvents was studied employing UV-vis-NIR spectroscopy. This indicates that doping and pyrrole-oligomers may improve the poor processibility of PPy. Its environmentally stable properties were characterized by thermogravimetric and differential thermal analysis (TG-DTA). The maximum room temperature conductivity of products is 8.01 S/cm using the four-probe technique. The pyrrole-oligomers have been determined by the analysis of molecular weight measurement, and X-ray photoelectron spectroscopy (XPS) and elemental analysis were employed to investigate the formation of DBSA-oligopyrrole complexes. Correspondingly, the structural properties of DBSA-oligopyrrole were studied by infrared spectroscopy (IR), X-ray diffraction (XRD), transmission electron micrographs (TEM), and scanning electron microscopy (SEM).

Journal Article↗

Respiratory flow in obstructed airways.

Chronic obstructive pulmonary disease (COPD) is one of the most common diseases in human community. The COPD always results in inflammation that leads to narrowing and obstruction of the airways. The obstructive airways have significant effect on respiratory flow. In order to understand the flow phenomenon in such obstructive airways, four three-dimensional four-generation lung models based on the 23-generation model of Weibel [1963. Morphometry of the Human Lung. Springer, Academic Press, Berlin, New York] are generated. The fully three-dimensional incompressible laminar Navier-Stokes equations are solved using computational fluid dynamics (CFD) solver on unstructured tetrahedral meshes. Therein, a symmetric four-generation airway model is served as the reference, the other three models are considered to be obstructed at each generation, respectively. The calculation results show that the obstructive airway has significant influence on the air flow in both up- and down-stream airways and it even results in flow separation in the conjunction region. The re-circulation cell blocks the air from entering the downstream branches. This may be the reason why COPD patients should breathe gently, and this also provides some valuable information for medicine powder deposition.

Airway Resistance↗

Synthesis of beta-hederin and Hederacolchiside A1: triterpenoid saponins bearing a unique cytotoxicity-inducing disaccharide moiety.

A facile synthetic approach toward oleanolic acid glycoside bearing alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl moiety, a unique oligosaccharide that strongly induces antitumor activity of oleanane-type triterpenoid saponins, was developed. Based on this approach beta-hederin (oleanolic acid 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside) was efficiently prepared from oleanolic acid through stepwise glycosylation in linear eight steps with 52% overall yield, while Hederacolchiside A1 (oleanolic acid 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranoside) in linear 13 steps with 20% overall yield.

Antineoplastic Agents↗

Isolation, structure elucidation, antioxidative and immunomodulatory properties of two novel dihydrocoumarins from Aloe vera.

Two new dihydrocoumarin derivatives, compounds 1 and 2, were isolated from Aloe vera. Their structures were determined by X-ray crystallographic diffraction analysis and extensive 1D, 2D NMR spectroscopic data. Both of them evidently showed antioxidant activity against superoxide and hydroxyl radicals. Only 1 obviously exhibited immunomodulatory activity in relation to increasing the phagocytic activity and stimulating the production of superoxide anions in the oxygen respiratory burst of rat peritoneal macrophages.

Aloe↗

Beta-2 adrenergic receptor gene (ADRB2) polymorphism and risk for lung adenocarcinoma: a case-control study in a Chinese population.

The incidence of lung adenocarcinoma (AC) has been increasing over recent decades. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent carcinogens and reproducibly induces a high incidence of lung AC in laboratory animals. In addition to its genotoxic effects, NNK has also epigenetic effects on lung cells by functioning as an agonist for beta adrenergic receptors and stimulating the signal pathways that lead to lung AC. Beta-2 adrenergic receptor (ADRB2) expressed on bronchial smooth muscle is a well-defined target for asthma treatment that has epidemiological implications in lung cancer development. And biochemical effect and pharmacogenetic relevance of regulatory and coding variants of ADRB2 have been well documented. Aiming to test whether the genetic variants of ADRB2 modify risk of lung AC, we compared the manifestation of three common single nucleotide polymorphisms (SNPs) of ADRB2 (G-1023A, G-654A, and A46G (Gly16Arg)) between 313 patients with lung AC and 321 controls. Overall association was not observed between risk and either individual of the three SNPs or their combined haplotypes. However, in the subgroup of young subjects < or =50 years old, significant association was observed for G-1023A (allele based OR, 1.82; 95% CI, 1.12-2.95), A46G (Gly16Arg) (allele based OR, 0.64; 95% CI, 0.40-1.03), and the haplotype A(-1023)A(46) (OR 2.62; 95% CI 1.30-5.27). Our results do not support a major independent role of ADRB2 polymorphisms in lung AC risk, suggesting that functional variants of other genes involved in the NNK epigenetic pathway of carcinogenesis should be investigated.

Asian People↗

The Scurfy mutation of FoxP3 in the thymus stroma leads to defective thymopoiesis.

The Scurfy mutation of the FoxP3 gene (FoxP3(sf)) in the mouse and analogous mutations in human result in lethal autoimmunity. The mutation of FoxP3 in the hematopoietic cells impairs the development of regulatory T cells. In addition, development of the Scurfy disease also may require mutation of the gene in nonhematopoietic cells. The T cell-extrinsic function of FoxP3 has not been characterized. Here we show that the FoxP3(sf) mutation leads to defective thymopoiesis, which is caused by inactivation of FoxP3 in the thymic stromal cells. FoxP3 mutation also results in overexpression of ErbB2 in the thymic stroma, which may be involved in defective thymopoiesis. Our data reveal a novel T cell-extrinsic function of FoxP3. In combination, the T cell-intrinsic and -extrinsic defects provide plausible explanation for the severity of the autoimmune diseases in the scurfy mice and in patients who have immunodysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome.

Animals↗

Characterization of reversed micelles of Cibacron Blue F-3GA modified Span 85 for protein solubilization.

The nonionic surfactant of sorbitan trioleate (Span 85) was modified with Cibacron Blue F-3GA (CB) as an affinity surfactant (CB-Span 85) to form affinity-based reversed micelles in n-hexane. The reversed micelles formed by the mixture of Span 85 and CB-Span 85 conjugate were extensively characterized in water content, hydrodynamic radius, and aggregation number. The results show that the water content and hydrodynamic radius of the reversed micelles were significantly increased by the introduction of CB ligands (CB-Span 85 conjugate), and the reversed micelles with CB-Span 85 conjugate had a wider aggregation number distribution than the Span 85 reversed micelles. Using lysozyme as a model protein, protein solubilization by the reversed micelles was investigated. Lysozyme solubilization increased significantly with the coupled CB concentration, indicating that the extraction was based upon the affinity interactions between lysozyme molecules and the CB ligand. High solubilization of lysozyme was obtained by the affinity-based reversed micelles of 62.7 mmol/L Span 85 with coupled CB higher than 0.25 mmol/L. Lysozyme recovery was carried out using a stripping solution of high ionic strength. The recovered lysozyme exhibited an activity equivalent to the native lysozyme and its secondary structure was also unchanged. The results indicate that the reversed micellar system would find potential application in protein separation.

Hexanes↗

CYP2J2*7 single nucleotide polymorphism in a Chinese population.

BACKGROUND: Human cytochrome P450 2J2 (CYP2J2) is the major arachidonic acid epoxygenase that plays important roles in the pathogenesis of a variety of diseases such as cardiovascular disorders and cancers, this P450 also plays a role in the metabolism of some antihistamine drugs. Variability of CYP2J2 gene is highly constrained except for at its proximal promoter a relatively common and functionally relevant single nucleotide polymorphism, namely CYP2J2*7, with allele frequency being 17%, 5.49%, 13%, and 4.23% in African, White, Asian, and Korean, respectively. Since this genetic variation differs strikingly between ethnic groups, we characterized the CYP2J2*7polymorphism in Chinese. METHODS: Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assays were used to genotype CYP2J2*7 in a sample of 384 healthy Chinese Han subjects. RESULTS: In this Chinese population, 20 (5.21%) heterozygotes and no homozygote for CYP2J2*7 allele were observed, and the allelic frequency was 2.60%. CONCLUSION: The CYP2J2*7 variant represents a relatively rare polymorphism in Chinese, with the allele frequency being comparable to that of Korean, but significantly lower than those of African and White groups. This data may be informative to design population-based association study of genetic predisposition to CYP2J2 related diseases and treatments.

Alleles↗

Elastic backscattering spectroscopic microscopy.

The spectral properties of elastic light-scattering signals have been shown to provide a wealth of information on nanostructures and microstructures. We present elastic backscattering spectroscopic microscopy that allows simultaneous acquisition of microscopic images and backscattering spectra at each pixel. Within a single homogeneous micrometer-scale particle we observe two distinct and highly localized spectral oscillation features that arise from different optical paths: (1) surface waves (e.g., the ripple structure) and (2) a not previously reported anomalous ripple structure that is due to the interference of waves scattered from front and back surfaces at the particle's center. We also demonstrate that the spectroscopic data can provide nanoscale structural information beyond what conventional microscopy reveals.

Equipment Design↗

Surface structures, photovoltages, and stability of n-Si(111) electrodes surface modified with metal nanodots and various organic groups.

The surface structures, photovoltages, and stability of n-Si(111) electrodes surface-modified with Pt nanodots and organic groups were studied in an I-/I3- redox electrolyte, using alkyls of varied chain length and those having a double bond and ester at the terminal as the organic groups. The n-Si was first modified with the organic groups, and then Pt was electrodeposited on it. Linear sweep voltammetry revealed that, for the modification with alkyls, the overvoltage for the Pt deposition became significantly larger with increasing alkyl chain length, though this does not necessarily hold for the modification with alkyls having a double bond and ester. Scanning electron microscopic inspection showed that the Pt particle density decreased and the particle size increased, with increasing alkyl chain length. The photovoltaic characteristics and stability for the n-Si electrodes modified with the organic groups were much improved by the Pt nanodot coating, though they became somewhat inferior with increasing alkyl chain length. On the basis of these results, it is concluded that surface alkylation at high coverage together with coating with small Pt nanodots gives efficient and stable n-Si electrodes.

Alkanes↗

A novel spin trap for targeting sulfhydryl-containing polypeptides.

A novel spin trap containing an iodoacetamide group has been synthesized and then used to target polypeptides, i.e. glutathione and bovine serum albumin, by which the resulting covalently bonded bioconjugates exhibit great potential for the application of spin trapping of transient radicals in biological systems.

Animals↗

Expression of early growth response factor-1 in rats with cerulein-induced acute pancreatitis and its significance.

AIM: To observe the expressions of early growth response factor-1 (Egr-1) and tissue factor (TF) in rats with cerulein-induced acute pancreatitis and to explore its significance. METHODS: A large dose of cerulein was used to create the experimental acute pancreatitis model in rats. The changes of Egr-1 mRNA and protein in rats were observed during 30 min to 4 h after the treatment and immunohistochemical method was used to observe the localized expression of Egr-1 in tissues. In addition to the mRNA expression of Egr-1 target gene, TF was also observed. A blank control group, and a bombesin-administered group were used for comparison. RESULTS: After the stimulation of a large dose of cerulein, the rats showed typical inflammatory changes of acute pancreatitis. Thirty minutes after the stimulation, the mRNA expression of Egr-1 in the pancreatic tissue reached its peak and then declined, while the expression of Egr-1 protein reached its peak 2 h after the stimulation. Histologically, 2 h after the stimulation, almost all pancreatic acinar cells had the expression of Egr-1 protein, which was focused in the nuclei. The mRNA expression of TF occurred 1 h after the stimulation and gradually increased within 4 h. However, a large dose of bombesin only stimulated the pancreatic tissue to produce a little mRNA expression of Egr-1 and no mRNA expression of Egr-1 protein and TF. CONCLUSION: Egr-1 as a pro-inflammatory transcription factor may play an important role in the pathogenesis of acute pancreatitis by modulating the expression of TF.

Acute Disease↗

Solvolysis procedures for the determination of bound residues of the mycotoxin deoxynivalenol in fusarium species infected grain of two winter wheat cultivars preinfected with barley yellow dwarf virus.

A trichloroacetic acid treatment at 140 degrees C for 40 min was successfully established as a suitable solvolysis procedure for the recovery of bound deoxynivalenol or its derivatives in Fusarium-infected plants. Deoxynivalenol itself was not decomposed in the procedure. The derivative 15-acetyl-deoxynivalenol was chosen as a model compound for setting free deoxynivalenol in an acid-catalyzed deesterification reaction, developing the method. This is the first report using a trichloroacetic acid solvolysis procedure as a sample incubation step to free bound deoxynivalenol and determine free from bound deoxynivalenol in the sample. Between 13 and 63% of the total deoxynivalenol consisted of nonextractable deoxynivalenol. Deoxynivalenol contents in grain of the susceptible cultivar "Agent" infected with Fusarium spp. were 12-24 times higher when compared to those for the corresponding moderately resistant cultivar "Petrus". The highest deoxynivalenol amounts were determined in grain infected with Fusarium spp. as well as simultaneously infected with BYDV. This solvolysis procedure may be of importance for distinguishing between resistant and susceptible plants and their ability to immobilize (bound) mycotoxins as a plant defense mechanism.

False Negative Reactions↗