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Yan Cheng

Publications and source records attributed to Yan Cheng.

At least 19 recordsLinked to original sources
PubMed2025

Metagenomic Analysis of the Tonsil Virome Highlights Its Diagnostic Potential for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease whose exact pathogenesis remains unclear, despite links to genetics, environmental factors, and microbial dysbiosis. Recent studies have highlighted the role of the microbiome in RA, yet the contribution of the tonsil virome remains unexplored. This study aims to investigate whether changes in the tonsil virome are associated with RA progression and assess its diagnostic potential. Using metagenomic data from 32 RA patients and 30 healthy controls (HCs), we identified 45 782 viral operational taxonomic units (vOTUs), with 14 341 classified as core vOTUs. RA patients exhibited significantly reduced virome richness and diversity, whereas Siphoviridae and Microviridae dominated both groups. Statistical analysis identified 235 RA-associated viral markers, including 13 enriched in RA and 222 in HCs. RA-enriched markers were primarily bacteriophages infecting Streptococcaceae, whereas HCs displayed more diverse viral-host interactions. Random forest models demonstrated strong discriminatory power of viral markers in distinguishing RA patients from HCs, achieving an AUC of 0.960, outperforming bacterial markers. Correlation analyses further linked viral markers to immune cell subsets, suggesting that tonsil virome alterations may influence immune dysregulation in RA. This study reveals significant changes in the tonsil virome of RA patients, highlighting its potential as a diagnostic tool and offering new insights into RA pathogenesis. These findings pave the way for future research into the virome's role in autoimmune diseases and therapeutic development.

Humans↗
PubMed2006

Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function.

We investigated the mechanisms by which inhibitors of prostaglandin G/H synthase-2 (PGHS-2; known colloquially as COX-2) increase the incidence of myocardial infarction and stroke. These inhibitors are believed to exert both their beneficial and their adverse effects by suppression of PGHS-2-derived prostacyclin (PGI(2)) and PGE(2). Therefore, the challenge remains to identify a mechanism whereby PGI(2) and PGE(2) expression can be suppressed while avoiding adverse cardiovascular events. Here, selective inhibition, knockout, or mutation of PGHS-2, or deletion of the receptor for PGHS-2-derived PGI(2), was shown to accelerate thrombogenesis and elevate blood pressure in mice. These responses were attenuated by COX-1 knock down, which mimics the beneficial effects of low-dose aspirin. PGE(2) biosynthesis is catalyzed by the coordinate actions of COX enzymes and microsomal PGE synthase-1 (mPGES-1). We show that deletion of mPGES-1 depressed PGE(2) expression, augmented PGI(2) expression, and had no effect on thromboxane biosynthesis in vivo. Most importantly, mPGES-1 deletion affected neither thrombogenesis nor blood pressure. These results suggest that inhibitors of mPGES-1 may retain their antiinflammatory efficacy by depressing PGE(2), while avoiding the adverse cardiovascular consequences associated with PGHS-2-mediated PGI(2) suppression.

Animals↗
PubMed2006

Selection demands versus association strength in the verb generation task.

Neuroimaging and neuropsychological data from Thompson-Schill and colleagues (Thompson-Schill, D'Esposito, Aguirre, and Farah, 1997; Thompson-Schill et al., 1998) showed that in the verb generation task, the left inferior frontal gyrus (left IFG) was more involved in a high-selection condition, in which the noun had two verb responses of equal association strength, than in a low-selection condition, in which the noun had only one strongly associated verb. They proposed that the left IFG was involved in selecting semantic information from competing alternatives. The present study compared verb generation in two high-selection conditions that varied in the association strength of the most frequently produced verbs. The results from neurally intact participants and a patient with a lesion that included the left IFG indicated that association strength between nouns and the most frequently produced verb, rather than competition during verb selection, affected verb generation. The degree of involvement of the left IFG may depend on the difficulty of verb retrieval as reflected in association strength.

Aged↗
PubMed2006

[Chiral separation of dipeptides by capillary electrophoresis].

Peptides are increasingly used as pharmaceutical agents. Many small peptides are the essential compounds in biological systems. Direct chiral separation of dipeptide derivatives using 9-(2-carbazole) ethyl chloroformate (CEOC) as the derivatizing agent by capillary electrophoresis (CE) with beta-cyclodextrin (beta-CD) and sodium deoxycholate (SDC) as chiral selectors has been developed. It has been well recognized that the combination of the binary selectors can enhance the selectivity and resolution instead of either beta-CD or SDC alone. The molar ratio of the binary chiral selectors, the buffer concentration and pH of Tris-H3PO4, organic modifier were studied and optimized. Complete chiral separations for 14 dipeptide derivatives using beta-CD and SDC as binary chiral selectors were obtained. The results indicated that each pair of D/L chiral resolution was more than 3.63, and the highest resolution for Gly-Ala was 43.14.

Calixarenes↗
PubMed2005

Are in vitro hepatitis B core promoter mutations important for clinical alterations in viral load?

In vitro studies of HBV core promoter mutations in hepatoma cell lines suggest that some mutations in core promoter transcription factor binding sites result in reduced core promoter activity and viral replication. We sought to validate this hypothesis using clinical samples with viral load differences before and after HBeAg seroconversion. A consensus sequence for transcription factor binding sites/regulatory regions was constructed based on published studies. Serum from two time points in 33 seroconverters and 10 interferon non-responders (controls) were utilized. Genotyping, HBV DNA quantification and direct sequencing of core promoter were performed. There were 216 new mutations following HBeAg seroconversion but few in controls. Mutations or mismatches to consensus transcription factor/regulatory region sequences clustered at nucleotide positions appeared genotype-specific, non-group specific or baseline mismatches and were discounted as having significant impact on viral replication. Only a few mutations in three seroconverters (9.1%) were specific, while 39.4% had no new mutations that could be attributed to reduction in viral load following HBeAg seroconversion. In 51.5% of patients, mutations were of uncertain significance because they occurred in demonstrated non-critical clustered nucleotide positions. Core promoter mutations post-seroconversion did not correlate with in vitro induced mutations that reduced the promoter activity.

Adult↗
PubMed2005

Antidepressant-like effects of BCEF0083 in the chronic unpredictable stress models in mice.

BACKGROUND: Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. METHODS: The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1, day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. RESULTS: Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma. CONCLUSIONS: This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.

Animals↗
PubMed2005

COX-2-derived prostacyclin modulates vascular remodeling.

Suppression of prostacyclin (PGI2) biosynthesis may explain the increased incidence of myocardial infarction and stroke which has been observed in placebo controlled trials of cyclooxygenase (COX)-2 inhibitors. Herein, we examine if COX-2-derived PGI2 might condition the response of the vasculature to sustained physiologic stress in experimental models that retain endothelial integrity. Deletion of the PGI2 receptor (IP) or suppression of PGI2 with the selective COX-2 inhibitor, nimesulide, both augment intimal hyperplasia while preserving luminal geometry in mouse models of transplant arteriosclerosis or flow-induced vascular remodeling. Moreover, nimesulide or IP deletion augments the reduction in blood flow caused by common carotid artery ligation in wild-type mice. Generation of both thromboxane (Tx)A2 and the isoprostane, 8, 12 -iso iPF(2alpha)-VI, are increased in the setting of flow reduction and the latter increases further on administration of nimesulide. Deletion of the TxA2 receptor (TP) reduces the hyperplastic response to nimesulide and carotid ligation, despite further augmentation of TP ligand production. Suppression of COX-2-derived PGI2 or deletion of IP profoundly influences the architectural response of the vasculature to hemodynamic stress. Mechanism based vascular remodeling may interact with a predisposition to hypertension and atherosclerosis in contributing to the gradual transformation of cardiovascular risk during extended periods of treatment with selective inhibitors of COX-2.

Animals↗
PubMed2005

Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturition.

Platelet activation is a hallmark of severe preeclampsia, and platelet PGH synthase 1-derived (PGHS1-derived) thromboxane A(2) (TxA(2)) has been implicated in its pathogenesis. However, genetic disruption of PGHS1 delays parturition. We created hypomorphic PGHS1 (PGHS1(Neo/Neo)) mice, in which the substantial but tissue-dependent variability in the inhibition of PGHS1-derived eicosanoids achieved by low-dose aspirin treatment is mimicked, to assess the relative impact of this strategy on hemostatic and reproductive function. Depression of platelet TxA(2) by 98% in PGHS1(Neo/Neo) mice decreased platelet aggregation and prevented thrombosis. Similarly, depression of macrophage PGE(2) by 75% was associated with selectively impaired inflammatory responses. PGF(2alpha) at 8% WT levels was sufficient to induce coordinated temporal oxytocin receptor (OTR) expression in uterus and normal ovarian luteolysis in PGHS1(Neo/Neo) mice at late gestation, while absence of PGHS1 expression in null mice delayed OTR induction and the programmed decrease of serum progesterone during parturition. Thus, extensive but tissue-dependent variability in PG suppression, as occurs with low-dose aspirin treatment, prevents thrombosis and impairs the inflammatory response but sustains parturition. PGHS1(Neo/Neo) mice provide a model of low-dose aspirin therapy that elucidates how prevention or delay of preeclampsia might be achieved without compromising reproductive function.

Animals↗
PubMed2005

Cardiovascular hazard and non-steroidal anti-inflammatory drugs.

Selective inhibitors of cyclooxygenase (COX)-2 depress prostacyclin (PGI(2)) without a concomitant inhibition of platelet COX-1-derived thromboxane (Tx)A(2). Experiments in gene-deleted mice have shown that ablation of the PGI(2) receptor (the IP) predisposes to an exaggerated response to agonists which elevate blood pressure, accelerate atherogenesis and induce thrombosis. Such a class-based effect would be expected to be modulated by the underlying risk of cardiovascular disease in patients, elements of drug exposure, such as dose, duration of action and duration of dosing, and inter-individual variability of drug response. Five placebo-controlled trials of three structurally distinct selective inhibitors of COX-2 have revealed an increased hazard of myocardial infarction and stroke consistent with a mechanism-based class-specific cardiovascular hazard. Sustained inhibition of platelet TxA(2) by aspirin affords cardiovascular benefit, despite concomitant inhibition of PGI(2). Although there is no information from randomized placebo-controlled trials, traditional non-steroidal anti-inflammatory drugs, such as naproxen, dicofenac and ibuprofen, might differ in their effects of cardiovascular biology.

Animals↗
PubMed2005

Effects of Atorvastatin on Th polarization in patients with acute myocardial infarction.

BACKGROUND: The development of heart failure after acute myocardial infarction (AMI) has been shown to be associated with inflammation, which is positively and negatively regulated by T helper (Th) 1 and Th2 lymphocytes, respectively. Several studies have indicated that statins can improve heart function after AMI. AIMS: To study the effects of atorvastatin on Th polarization in patients with AMI. METHODS: Peripheral blood mononuclear cells were collected from 20 patients with AMI treated with oral atorvastatin (10 mg/d, group AMI-A) and 18 patients with AMI (group AMI-C) who did not receive treatment with statins. Cytokine-producing Th lymphocytes were quantified by 3-color flow cytometry. After in vitro culturing in the presence or absence of atorvastatin (0, 0.3, 1 and 3 micromol/L) for 6 days, cytokine-producing Th lymphocytes were quantified again in AMI-C group. RESULTS: The ratio of IFN-gamma-producing T cells was significantly higher in AMI-C group (17.8% +/- 6.4%) than in the AMI patients treated with oral atorvastatin (AMI-A, 13.1% +/- 4.6%). In vitro culturing with atorvastatin significantly reduced Th1 development in the AMI-C group. There was no significant difference on the frequencies of interleukin (IL)-4-producing T cells between each group. CONCLUSIONS: Atorvastatin can reduce Th1 development but has no effect on Th2 cell-functions in AMI patients. Our findings suggest that atorvastatin can regulate the polarization of Th1/Th2, this may be one of the mechanisms through which atorvastatin improves heart function after AMI.

Atorvastatin↗
PubMed2005

Peripheral clocks and the regulation of cardiovascular and metabolic function.

Circadian rhythms generated by cell autonomous biological clocks allow for the appropriate temporal synchronization of physiology and behavior, optimizing the efficiency of biological systems. Circadian oscillators and functions have been uncovered in both central and peripheral tissues. This article describes methodology, experimental design, and technical challenges pertaining to studies of circadian rhythms in the periphery. Experimental approaches are focused upon revealing the role of peripheral clocks in cardiovascular and metabolic function using in vitro and in vivo techniques.

ARNTL Transcription Factors↗
PubMed2004

Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressure.

BACKGROUND: The proinflammatory and vascular actions of cysteinyl leukotrienes (CysLTs) are mediated by 2 receptors: cysteinyl leukotriene 1 receptor (CysLT1R) and cysteinyl leukotriene 2 receptor (CysLT2R). However, the distinct contribution of CysLT2R to the vascular actions of CysLTs has not been addressed. METHODS AND RESULTS: We generated an endothelial cell-specific human CysLT2R (EC-hCysLT2R) transgenic (TG) mouse model using the Tie2 promoter/enhancer. Strong expression of hCysLT2R in TG lung and endothelial cells, detected by real-time polymerase chain reaction, markedly enhanced CysLT-stimulated intracellular calcium mobilization compared with endogenous expression in cells from nontransgenic mice. The permeability response to exogenous LTC4 and to endogenous CysLTs evoked by passive cutaneous anaphylaxis was augmented in TG mice. The rapid, systemic pressor response to intravenous LTC4 was also diminished in TG mice coincidentally with augmented production of nitric oxide. CONCLUSIONS: The development of EC-hCysLT2R mice has permitted detection of distinct vascular effects of CysLTs, which can be mediated via the CysLT2R in vivo.

Animals↗
PubMed2004

The zebrafish Pard3 ortholog is required for separation of the eye fields and retinal lamination.

The vertebrate retina develops from a sheet of neuroepithelial cells. Because adherens and tight junctions are critical for epithelial and neuronal differentiation in a variety of eukaryotic systems, we examined the role of Par-3, a PDZ scaffold protein that is critical in cellular membrane junction formation. We cloned the zebrafish Par-3 ortholog (pard3), which encodes two Pard3 proteins (150 and 180 kDa) that differ in their carboxyl-terminus. Immunohistochemistry revealed that Pard3 localized to the apical region of the retinal and brain neuroepithelium, partially overlapping the adherens junction-associated actin bundles. After retinal lamination, the Pard3 protein was restricted to the outer limiting membrane and the outer and inner plexiform layers in the retina. Reducing Pard3 expression with antisense morpholinos caused loss of the retinal pigmented epithelia, disruption of retinal lamination, and cell death in the ventral diencephalon, which resulted in cyclopia. Overexpressing Pard3 by injection of wild-type pard3 mRNA resulted in cyclopia and eyeless embryos. Thus, Pard3 plays a critical role in the origination and separation of zebrafish eye fields and retinal lamination.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Novel dominant rhodopsin mutation triggers two mechanisms of retinal degeneration and photoreceptor desensitization.

A variety of rod opsin mutations result in autosomal dominant retinitis pigmentosa and congenital night blindness in humans. One subset of these mutations encodes constitutively active forms of the rod opsin protein. Some of these dominant rod opsin mutant proteins, which desensitize transgenic Xenopus rods, provide an animal model for congenital night blindness. In a genetic screen to identify retinal degeneration mutants in Drosophila, we identified a dominant mutation in the ninaE gene (NinaE(pp100)) that encodes the rhodopsin that is expressed in photoreceptors R1-R6. Deep pseudopupil analysis and histology showed that the degeneration was attributable to a light-independent apoptosis. Whole-cell recordings revealed that the NinaE(pp100) mutant photoreceptor cells were strongly desensitized, which partially masked their constitutive activity. This desensitization primarily resulted from both the persistent binding of arrestin (ARR2) to the NINAE(pp100) mutant opsin and the constitutive activity of the phototransduction cascade. Whereas mutations in several Drosophila genes other than ninaE were shown to induce photoreceptor cell apoptosis by stabilizing a rhodopsin-arrestin complex, NinaE(pp100) represented the first rhodopsin mutation that stabilized this protein complex. Additionally, the NinaE(pp100) mutation led to elevated levels of G(q)alpha in the cytosol, which mediated a novel retinal degeneration pathway. Eliminating both G(q)alpha and arrestin completely rescued the NinaE(pp100)-dependent photoreceptor cell death, which indicated that the degeneration is entirely dependent on both G(q)alpha and arrestin. Such a combination of multiple pathological pathways resulting from a single mutation may underlie several dominant retinal diseases in humans.

Animals↗
PubMed2004

Thromboxane A2 receptor agonists antagonize the proangiogenic effects of fibroblast growth factor-2: role of receptor internalization, thrombospondin-1, and alpha(v)beta3.

Thromboxane (TX) A2 is released from multiple cell types and is a prime mediator of the pathogenesis of many vascular events, including angiogenesis. Endothelial cells express TXA2 receptors (TP) but the effects of TP stimulation on angiogenesis remain controversial. In this study, we show that stimulation of endothelial cell TP impairs ligand-induced FGF receptor internalization and consequently abrogates FGF-2-induced endothelial cell migration in vitro and angiogenesis in vivo. Prevention of FGF-2-induced angiogenesis was associated with expression of the TPbeta isoform. The deficit in FGFR1 internalization was mediated through activation of TPbeta preventing the FGF-2-mediated decrease in p53 expression, thus enhancing thrombospondin-1 (TSP-1) release from EC and reducing FGFR1 internalization. Once released TSP-1 interacted with the alpha(v)beta3 integrin on the EC surface. On stimulation, FGFR1 and alpha(v)beta3 were found to associate in a complex. We determined that complex formation was important for receptor internalization as conditions that inhibit FGFR1 internalization, such as inappropriate ligation of alpha(v)beta3 by either TSP-1 or a neutralizing antibody, disrupted the complex. These results establish a novel role for isoform specific regulation of angiogenesis by TP, provide the first functional significance for the existence of two TP isoforms in humans, and clarify the mechanism by which TP signaling regulates FGFR1 kinetics and signaling.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2004

Extracorporeal whole blood immunoadsorption of autoimmune myasthenia gravis by cellulose tryptophan adsorbent.

Whole blood immunoadsorption (WBIA) system, using an adsorbent to remove pathogenic antibodies of myasthenia gravis (MG), was studied. Cellulose-tryptophan adsorbent was synthesized and its adsorption capacity of binding with acetylcholine receptor in the plasma of MG patient was evaluated. Experimental autoimmune myasthenia gravis (EAMG) rabbits were induced by Ta183-200 peptide. The rabbits underwent extracorporeal whole blood adsorption for 2 h. Results showed no significant damages on blood cells and no changes in the concentration of electrolytes. Total protein decreased by 12.0% (P < 0.05), and globulin protein decreased 23.9 +/- 5.6% (P < 0.05). The mean overall removal of antibodies against Ta183-200 was 41.12%. The percentage of decrement of compound muscle action potential in 3, 5, 10Hz of EAMG rabbits all dropped down after the treatment. In conclusion, the adsorbent is biocompatible, was safe for whole blood immunoadsorption, and can remove antibodies in an MG patient effectively. Whole blood immunoadsorption improved clinical manifestation and neuromuscular function of the EAMG rabbits.

Animals↗
PubMed2003

In vitro, in vivo studies of a new amphiphilic adsorbent for the removal of low-density lipoprotein.

A new amphiphilic adsorbent for the removal of low-density lipoprotein (LDL) was prepared according to the literature (Artif. Cells Blood Subs., Immob. Biotechnol. 30 (4) (2002) 285). The effects of sulfonation and grafting time of cholesterol on the swelling property of adsorbent were studied. When sulfonation and grafting time of cholesterol was 3 and 5 h, respectively, the amphiphilic adsorbent had a high adsorption capacity for LDL without significantly adsorbing high-density lipoprotein. The adsorption capacity of the adsorbent for the removal of LDL, total cholesterol (TC) and TG was 1.916, 2.132, 1.349 mg/ml, respectively. Hyperlipidemia rabbits were developed by feeding with fodder containing high content of cholesterol or yolk, which was then perfused with an optimal amount of amphiphilic adsorbent. After 2 h hemoperfusion, the LDL levels decreased from 3.619+/-0.354 to 0.724+/-0.07 mmol/l, which showed that the adsorbent could effectively remove LDL without side effect.

Adsorption↗