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Ying Wan

Publications and source records attributed to Ying Wan.

At least 19 recordsLinked to original sources
PubMed2024

Integrated Multi-Omics Analyses Reveal Lipid Metabolic Signature in Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease and the second leading cause of disability worldwide. Single-omics analyses are far from elucidating the complex mechanisms of lipid metabolic dysfunction in OA. This study identified a shared lipid metabolic signature of OA by integrating metabolomics, single-cell and bulk RNA-seq, as well as metagenomics. Compared to the normal counterparts, cartilagesin OA patients exhibited significant depletion of homeostatic chondrocytes (HomCs) (P&#xa0;=&#xa0;0.03) and showed lipid metabolic disorders in linoleic acid metabolism and glycerophospholipid metabolism which was consistent with our findings obtained from plasma metabolomics. Through high-dimensional weighted gene co-expression network analysis (hdWGCNA), weidentified PLA2G2A as a hub gene associated with lipid metabolic disorders in HomCs. And an OA-associated subtype of HomCs, namely HomC1 (marked by PLA2G2A, MT-CO1, MT-CO2, and MT-CO3) was identified, which also exhibited abnormal activation of lipid metabolic pathways. This suggests the involvement of HomC1 in OA progression through the shared lipid metabolism aberrancies, which were further validated via bulk RNA-Seq analysis. Metagenomic profiling identified specific gut microbial species significantly associated with the key lipid metabolism disorders, including Bacteroides uniformis (P&#xa0;<&#xa0;0.001, R&#xa0;=&#xa0;-0.52), Klebsiella pneumonia (P&#xa0;=&#xa0;0.003, R&#xa0;=&#xa0;0.42), Intestinibacter_bartlettii (P&#xa0;=&#xa0;0.009, R&#xa0;=&#xa0;0.38), and Streptococcus anginosus (P&#xa0;=&#xa0;0.009, R&#xa0;=&#xa0;0.38). By integrating the multi-omics features, a random forest diagnostic model with outstanding performance was developed (AUC&#xa0;=&#xa0;0.97). In summary, this study deciphered the crucial role of a integrated lipid metabolic signature in OA pathogenesis, and established a regulatory axis of gut microbiota-metabolites-cell-gene, providing new insights into the gut-joint axis and precision therapy for OA.

Humans↗
PubMed2007

Porous polylactide/chitosan scaffolds for tissue engineering.

Novel porous scaffolds were fabricated using biodegradable polylactide/chitosan blends. A combinational technique involving solvent-extracting, liquid-solid separation, and freeze-drying paths were employed. The processing parameters were optimized in order to produce desired porous scaffolds and thus obtained scaffolds showed well distributed and interconnected porous structures with controllable porosities varying from around 50-85% and regulative pore sizes being distributed within a region between 2 and 190 microm. These scaffolds exhibited remarkably improved hydrophilicity based on the measurements for their swelling index. The results obtained from in vitro incubation of scaffolds in phosphate buffered saline solutions at 37 degrees C during various periods up to 10 weeks indicated that chitosan component inside the scaffolds, on the one hand, effectively buffered the acidic degradation products of polylactide/chitosan scaffolds and on the other hand, the degradation of the scaffolds was also conspicuously delayed. These porous scaffolds maintained well-defined compressive mechanical properties and by well-blending polylactide with chitosan component, improved toughness on the resultant porous scaffolds was also observed.

Biocompatible Materials↗
PubMed2006

Triconstituent co-assembly to ordered mesostructured polymer-silica and carbon-silica nanocomposites and large-pore mesoporous carbons with high surface areas.

Highly ordered mesoporous polymer-silica and carbon-silica nanocomposites with interpenetrating networks have been successfully synthesized by the evaporation-induced triconstituent co-assembly method, wherein soluble resol polymer is used as an organic precursor, prehydrolyzed TEOS is used as an inorganic precursor, and triblock copolymer F127 is used as a template. It is proposed for the first time that ordered mesoporous nanocomposites have "reinforced concrete"-structured frameworks. By adjusting the initial mass ratios of TEOS to resol, we determined the obtained nanocomposites possess continuous composition with the ratios ranging from zero to infinity for the two constituents that are "homogeneously" dispersed inside the pore walls. The presence of silicates in nanocomposites dramatically inhibits framework shrinkage during the calcination, resulting in highly ordered large-pore mesoporous carbon-silica nanocomposites. Combustion in air or etching in HF solution can remove carbon or silica from the carbon-silica nanocomposites and yield ordered mesoporous pure silica or carbon frameworks. The process generates plenty of small pores in carbon or/and silica pore walls. Ordered mesoporous carbons can then be obtained with large pore sizes of approximately 6.7 nm, pore volumes of approximately 2.0 cm(3)/g, and high surface areas of approximately 2470 m(2)/g. The pore structures and textures can be controlled by varying the sizes and polymerization degrees of two constituent precursors. Accordingly, by simply tuning the aging time of TEOS, ordered mesoporous carbons with evident bimodal pores at 2.6 and 5.8 nm can be synthesized.

Journal Article↗
PubMed2006

"Host-guest" chemistry in the synthesis of ordered nonsiliceous mesoporous materials.

On the basis of the consideration of "host-guest" chemistry, the interactions between guest molecules are highlighted in the synthesis of nonsiliceous mesoporous materials by the "soft-template" and "hard-template" approaches. A generalized "acid-base pair" concept is utilized in selecting appropriate guest molecules to prepare highly ordered mesoporous metal oxides, phosphates, and borates with diversified structures. Mesoscopically ordered polymer and carbon frameworks with uniformly large pore sizes are derived from the self-assembly of an organic surfactant with an organic guest. Properly building the guest unit and decorating the host are important in replicating ordered nonsiliceous single-crystal nanoarrays. Outlooks on the potential possibilities for synthesizing ordered mesoporous nonsiliceous materials are presented as well.

Journal Article↗
PubMed2006

Biodegradable polylactide/chitosan blend membranes.

Biodegradable blend membranes based on polylactide and chitosan with various compositions were prepared via a two-step processing pathway. In the first step, solutions of each component were properly mixed and cast into a gelatinous membrane, and in the second step, the obtained membrane was immersed into a mixed solution for the solvent extraction followed by a drying procedure to finally generate a well-blended membrane. An acetic acid-acetone solvent system was selected for poly(DL-lactide)/chitosan membranes, and another solvent system for poly(L-lactide)/chitosan membranes consisted of acetic acid and dimethyl sulfoxide. Some processing parameters, such as the concentration of component solutions and the composition ratio of mixed solvents and extraction solvents, were optimized by primarily considering whether the directly visible phase separation occurred during the processing procedures. Morphologies of these blend membranes were viewed using SEM. It was found that the processing parameters exerted quite notable impacts on the morphology of the membranes. The hydrophilicity of membranes was examined by measuring their water contact angle and swelling index. These blend membranes were also investigated for their miscibility using IR spectra, X-ray diffractograms, TG, DSC, and dynamic mechanical analysis methods. Although the presence of phase separation at a microscopic level was detected for these membranes, pronounced interactions between components were confirmed. The obtained results shown that some membranes prepared under optimized processing conditions had a partially miscible structure.

Acetic Acid↗
PubMed2006

Long-term effects of a losartan- compared with an atenolol-based treatment regimen on carotid artery plaque development in hypertensive patients with left ventricular hypertrophy: ICARUS, a LIFE substudy.

In the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study, there was a 25% risk reduction for stroke with angiotensin receptor blocker-based therapy (losartan) as compared with beta-blocker-based therapy (atenolol) despite comparable blood pressure reductions. This substudy examines treatment effects on the amount and density of atherosclerotic lesions in the common carotid arteries and the carotid bulb in 81 patients during 3 years of treatment. There were no statistically significant changes in the amount of carotid plaque in patients treated with losartan compared with an atenolol-based treatment program. A statistically nonsignificant increase in plaque density and index (average of plaque amount and density) was seen in the atenolol group compared with those treated with losartan. The small number of patients evaluated may have limited the power to detect a difference in outcome. The difference in carotid plaque index increase between the treatment groups during 3 years of treatment could not be statistically linked to specific treatments in the present substudy.

Adrenergic beta-Antagonists↗
PubMed2006

Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study.

OBJECTIVE: Our current aims were to investigate whether 1) baseline urinary albumin-to-creatinine ratio (UACR) predicted cardiovascular outcomes, 2) changes in UACR differed between treatments, 3) benefits of losartan were related to its influence on UACR, and 4) reduction in albuminuria reduced cardiovascular events. RESEARCH DESIGN AND METHODS: In 1,063 patients with diabetes, hypertension, and left ventricular hypertrophy, UACR was measured for a mean of 4.7 years. The primary composite end point included cardiovascular death, myocardial infarction, and stroke. Cox models were run including and excluding baseline and time-varying UACR. RESULTS: Increasing baseline albuminuria related to increased risk for cardiovascular events. Reductions in UACR at years 1 and 2 were approximately 33% for losartan vs. 15% for atenolol (P < 0.001). Benefits of losartan seem to be most prominent in patients with the highest level of baseline UACR, although treatment by albuminuria interaction was only significant for total mortality. Approximately one-fifth of the superiority of losartan was explained by the greater reduction of albuminuria. Risk of the primary end point was related to the in-treatment UACR. CONCLUSIONS: Lowering of albuminuria in patients with hypertension and diabetes appears to be beneficial and should be the subject of additional study in future clinical trials.

Aged↗
PubMed2005

Comprehensive antibody epitope mapping of the nucleocapsid protein of severe acute respiratory syndrome (SARS) coronavirus: insight into the humoral immunity of SARS.

BACKGROUND: The epidemic outbreak of severe acute respiratory syndrome (SARS) posed a worldwide threat to public health and economic stability. Although the pandemic has been contained, concerns over its recurrence remain. It is essential to identify specific diagnostic agents and antiviral vaccine candidates to fight this highly contagious disease. METHODS: We generated 14 monoclonal antibodies (mAbs) specific to the SARS coronavirus (SARS-CoV) nucleocapsid (N) protein and used these to thoroughly map the N protein antigenic determinants. We identified the immunodominant antigenic sites responsible for the antibodies in sera from SARS patients and antisera from small animals and differentiated the linear from the conformational antibody-combining sites comprising the natural epitopes by use of yeast surface display. RESULTS: We identified 5 conformational and 3 linear epitopes within the entire N protein; 3 conformational and 3 linear epitopes were immunodominant. The antibody responses to the N protein fragments in mammalian sera revealed that 3 regions of the N protein are strong antigenic domains. We expanded the specificity of the N protein epitope and identified 4 novel conformational epitopes (amino acids 1-69, 68-213, 212-341, and 337-422). CONCLUSION: The antigenic structures identified for the SARS-CoV N protein, the epitope-specific mAbs, and the serum antibody profile in SARS patients have potential use in the clinical diagnosis and understanding of the protective immunity to SARS-CoV.

Adult↗
PubMed2005

Analysis of bleeding complications associated with glycoprotein IIb/IIIa receptors blockade in patients with high-risk acute coronary syndromes: insights from the PRISM-PLUS study.

We aim to characterize the hemorrhagic complications and predictors of increased bleeding risk in a population of patients with high-risk acute coronary syndromes (ACS), enrolled in the PRISM-PLUS study. Patients treated with heparin plus tirofiban had more bleeding events compared to patients treated with heparin alone. No significant increase in major bleeding, thrombocytopenia, blood loss and blood products transfusions was observed among the patients who received the combination therapy. Several clinical variables were independently associated with increased risk of bleeding for both treatment groups: advanced age, lower body weight, female gender, decreased creatinine clearance (<30 ml/min). Females, patients with impaired renal function, patients requiring percutaneous coronary intervention (PCI), especially prolonged PCI (>100 min duration) or coronary artery bypass surgery (CABG) were at risk for increased major bleeding complications. Increased blood loss was also found in females, patients with elevated diastolic blood pressure, PCI, duration of PCI>100 min or CABG. No incremental risk was detected with the addition of tirofiban to heparin in patients at risk for major bleeding or increased blood loss. We concluded that identification of patients with high-risk ACS, at risk for bleeding complications and blood loss can be done with specific clinical variables. Tirofiban added to heparin increased minor hemorrhagic complications. Although there was no significant increase in major bleeding, thrombocytopenia and blood transfusions with the combination of tirofiban plus heparin, the power to detect a statistically significant difference in these endpoints was limited by the small number of events.

Aged↗
PubMed2005

Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study.

Few data are available to clarify whether changes in albuminuria over time translate to changes in cardiovascular risk. The aim of the present study was to examine whether changes in albuminuria during 4.8 years of antihypertensive treatment were related to changes in risk in 8206 patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Urinary albumin/creatinine ratio (UACR) was measured at baseline and annually. Time-varying albuminuria was closely related to risk for the primary composite end point (ie, when UACR decreased during treatment, risk was reduced accordingly). When the population was divided according to median baseline value (1.21 mg/mmol) and median year 1 UACR (0.67 mg/mmol), risk increased stepwise and significantly for the primary composite end point from those with low baseline/low year 1 (5.5%), to low baseline/high year 1 (8.6%), to high baseline/low year 1 (9.4%), and to high baseline/high year 1 (13.5%) values. Similar significant, stepwise increases in risk were seen for the components of the primary composite end point (cardiovascular mortality, stroke, and myocardial infarction). The observation that changes in UACR during antihypertensive treatment over time translated to changes in risk for cardiovascular morbidity and mortality was not explained by in-treatment level of blood pressure. We propose that monitoring of albuminuria should be an integrated part of the management of hypertension. If albuminuria is not decreased by the patient's current antihypertensive and other treatment, further intervention directed toward blood pressure control and other modifiable risks should be considered.

Aged↗
PubMed2005

Cross-presentation of phage particle antigen in MHC class II and endoplasmic reticulum marker-positive compartments.

It has been shown that exogenous antigens can access the MHC class I pathway of professional antigen-processing cells. However, details as to how the MHC class I-peptide complex forms in the presentation pathway are still poorly understood. Here we used MHC class I-peptide-specific antibodies to investigate the formation and intracellular location of class I-peptide complexes in macrophages. We observed that the formation of class I-peptide complexes occurs within a few hours and lasts for another few hours on the cell surface of macrophages following loading with filamentous phage particles. The class I-peptide complexes in the process were co-localized with MHC class II molecules and endocytic system markers. Moreover, endosomal compartments containing class I-peptide complexes were found within intracellular organelles stained by DiOC6 and calnexin. In addition, the cross-presentation of phage particles was transporter associated with antigen processing (TAP)-dependent and sensitive to proteasome inhibitors and NH(4)Cl. These data suggest that endocytosed phage particles may be processed and cross-presented in organelles positive for phagosome and endoplasmic reticulum (ER) markers via a classical ER MHC class I loading mechanism.

Ammonium Chloride↗
PubMed2005

Porous-conductive chitosan scaffolds for tissue engineering II. in vitro and in vivo degradation.

Porous-conductive chitosan scaffolds were fabricated by blending conductive polypyrrole (PPy) particles with chitosan solution and employing an improved phase separation method. In vitro and in vivo degradation behaviors of these scaffolds were investigated. In the case of in vitro degradation, an enzymatic degradation system was employed and lysozyme was used as a working enzyme. Meanwhile, the degradation products of scaffolds, glucosamine and N-acetyl-glucosamine, were also analyzed with a HPLC method. In vivo degradation of scaffolds was performed by subcutaneously implanting these scaffolds in rat for pre-scheduled time intervals. In the both cases, the weight-loss of scaffolds was monitored during the whole degradation process for evaluating the degradation of scaffolds. The changes in conductivity of scaffolds afterin vitro or in vivo degradation were also measured using a four-point technique. It was observed that the pore parameters of scaffolds themselves could significantly influence the degradation behaviors of scaffolds but the PPy content in the scaffolds seemed not to impart its effect to the degradation of scaffolds. Degradation dynamics of scaffolds and conductivity measurements indicated that these scaffolds shown fairly different behaviors in their in vitro and in vivo degradation process. According to the results obtained from in vitro and in vivo degradation of scaffolds and based on some requirements of practical tissue engineering application, it was suggested that the PPy content in the scaffold should be slightly higher than 3 wt.% but lower than 6 wt.%.

Animals↗
PubMed2005

H-2 Kd-restricted hepatitis B virus-derived epitope whose specific CD8+ T lymphocytes can produce gamma interferon without cytotoxicity.

It is necessary to evaluate the cytokine secretion status of CD8+ T lymphocytes and elucidate the factors influencing cytokine secretion, because the secretion of cytokines is also an important feature of CD8+ T lymphocytes, and the cytokines usually play critical roles in the outcome of diseases. We showed here that peptide AYRPPNAPI, derived from the core antigen of hepatitis B virus (HBV), could bind to H-2 Kd and induce primed splenocytes from HBcAg expression plasmid-immunized mice to produce gamma interferon (IFN-gamma) in H-2 Kd- and CD8-dependent manners instead of in a CD4-dependent manner. The induced cells were mainly CD3 and CD8 positive but had no cytotoxic effect on the corresponding target cells. When administered into HBV transgenic mice, these cells can decrease the serum HBV load without causing liver damage. These results suggest that this peptide is a special kind of CD8+ T-cell epitope, for which specific CD8+ T cells can produce IFN-gamma when antigenic stimulation is encountered but which have no cytotoxic effect on the corresponding target cells both in vitro and in HBV transgenic mice. This phenomenon indicates initially that the functional mechanisms of CD8+ T cells can be determined by their epitope specificity, which may be associated with the development of epitope-based immunotherapeutic approaches for infectious diseases and tumors.

Animals↗
PubMed2004

Oxcarbazepine in painful diabetic neuropathy: a randomized, placebo-controlled study.

In this multicentre, placebo-controlled, 16-week trial, the efficacy and safety of oxcarbazepine monotherapy in patients with neuropathic pain of diabetic origin was evaluated. Eligible patients had a 6-month to 5-year history of neuropathic pain symptoms of diabetic origin and a pain rating of > or =50 units on the visual analogue scale (VAS). Oxcarbazepine was initiated at a dose of 300 mg/day and titrated to a maximum dose of 1800 mg/day. In total, 146 patients (oxcarbazepine, n=69; placebo, n=77) were randomized. After 16 weeks, oxcarbazepine-treated patients experienced a significantly larger decrease in the average change in VAS score from baseline compared with placebo (-24.3 vs. -14.7 units, respectively; p=0.01). The reduction from baseline in mean VAS score for oxcarbazepine-treated patients was of a greater magnitude than placebo as early as week 2 (-8.0 vs. -4.7; p<0.05). A significantly greater proportion of oxcarbazepine-treated patients experienced a >50% reduction from baseline in VAS score at the end of treatment compared with placebo (35.2% vs. 18.4%, respectively; p=0.0156; number needed to treat=6.0). Global assessment of therapeutic effect rating was improved in more oxcarbazepine patients than placebo patients (48% vs. 22%, respectively; p=0.0025). Patients on oxcarbazepine were awakened less frequently due to pain than patients on placebo. Most adverse events were mild to moderate in severity, transient, and in line with the known tolerability profile of oxcarbazepine. These observations suggest that oxcarbazepine monotherapy, pending additional trials, may be efficacious and may provide clinically meaningful pain relief in patients with neuropathic pain of diabetic origin.

Adolescent↗
PubMed2004

Effective induction of antitumor immunity by immunization with plasmid DNA encoding TRP-2 plus neutralization of TGF-beta.

Plasmid DNA vaccine is an appealing cancer immunotherapy. However, it is a weak immunogen and immunization with plasmid DNA encoding self-antigens, such as melanoma-associated antigens, could not induce antitumor immunity because of tolerance. In this study, we investigated the feasibility of using a plasmid DNA encoding Xenopus laevis transforming growth factor-beta 5 (aTGF-beta5) as an immunogen to induce neutralizing antibodies against murine TGF-beta1 (mTGF-beta1) and thus enhance the efficacy of plasmid DNA vaccine encoding murine tyrosinase-related protein 2 (mTRP-2) through neutralization of TGF-beta. The results showed that immunization with aTGF-beta5 resulted in the generation of mTGF-beta1-neutralizing antibodies, and immunization with a combination of aTGF-beta5 and mTRP-2 induced specific cytotoxic T lymphocytes (CTLs). On the contrary, immunization with mTRP-2 alone could not elicit the CTL response. Moreover, immunization of C57BL/6 wild-type mice with a combination of aTGF-beta5 and mTRP-2 induced the protective and therapeutic antitumor immunity to B16F10 melanoma, whereas the antitumor activity was abrogated in both CD4-deficient mice and CD8-deficient mice on the C57BL/6 background. Our results indicate that immunization with aTGF-beta5 is capable of breaking immune tolerance and induces mTGF-beta1-neutralizing antibodies. Neutralization of TGF-beta can enhance the efficacy of DNA vaccine encoding mTRP-2 and the induction of antitumor immunity by this immunization strategy is associated with CD4+ and CD8+ T cells.

Animals↗
PubMed2004

Porous-conductive chitosan scaffolds for tissue engineering, 1. Preparation and characterization.

Novel porous-conductive chitosan scaffolds were fabricated by incorporating conductive polypyrrole (PPy) particles into a chitosan matrix and employing a phase separation technique to build pores inside the scaffolds. Conductive polypyrrole particles were prepared with a microemulsion method using FeCl3 as a dopant. The preparation conditions were optimized to obtain scaffolds with controlled pore size and porosity. The conductivity of the scaffolds was investigated using a standard four-point probe technique. It was found that several kinds of scaffolds showed a conductivity close to 10(-3) S.cm(-1) with a low polypyrrole loading of around 2 wt.-%. The main mechanical properties, such as tensile strength, breaking elongation and Young's modulus of the scaffolds, were examined both in the dry and in the hydrated states. The results indicated that a few different kinds of scaffolds exhibited the desired mechanical strength for some tissue engineering applications. The miscibility of polypyrrole and chitosan was also evaluated using a dynamic mechanical method. The presence of significant phase separation was detected in non-porous PPy/chitosan scaffolds but enhanced miscibility in porous PPy/chitosan scaffolds was observed.

Biocompatible Materials↗
PubMed2004

In vivo evaluation of a novel electrically conductive polypyrrole/poly(D,L-lactide) composite and polypyrrole-coated poly(D,L-lactide-co-glycolide) membranes.

This study evaluated the in vivo biocompatibility and biodegradation behavior of a novel polypyrrole (PPy)/poly(D,L-lactide) (PDLLA) composite and PPy-coated poly(D,L-lactide-co-glycolide) membranes. Test membranes were implanted subcutaneously in rats for 3-120 days. The biocompatibility was assessed by quantifying the alkaline and acid phosphatase secretion, the immunohistochemical staining of the ED-2-positive macrophages, and the histology at the tissue/material interface. The degradation was investigated using scanning electron microscopy. Pure PDLLA and poly(D,L-lactide-co-glycolide) membranes were used as references, whereas expanded polytetrafluoroethylene and a commercial styrene-butadiene rubber were used as controls. The enzyme activity of the PPy-containing specimens was shown to be similar to that of the references. The histological findings were consistent with the enzymatic results, showing a mild-to-moderate acute inflammation followed by a resolution of the inflammatory response with a decrease in inflammatory cells for each biodegradable membrane. The tissue reactions to the PPy, which was either in the form of nanoparticles or surface coating, were comparable to the response to the neighboring biodegradable materials. Elevated ED-2-positive macrophage populations appeared as early as day 3 in the loose connective tissue surrounding the implants. The density of these populations was related to the degree of inflammation. Scanning electron microscopy showed that the degradation of the PPy/PDLLA composite was not affected by the presence of PPy.

Acid Phosphatase↗