Biomedical subjects

Ying Zheng

Publications and source records attributed to Ying Zheng.

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↗

PubMed2007

Iron chelation study in a normal human hepatocyte cell line suggests that tumor necrosis factor receptor-associated protein 1 (TRAP1) regulates production of reactive oxygen species.

Iron is an essential component of many proteins, and has crucial roles in the proper functioning of proteins involved in cellular respiration, proliferation, and differentiation. It has been recently reported that the deferoxamine (DFO), an iron chelator, induces mitochondrial dysfunction, characterized by an attenuation of oxidative phosphorylation, as well as senescence-like cellular morphology. However, the effects of DFO on mitochondrial heat shock proteins (HSPs) remain poorly understood. In this study, we examined the effect of DFO on tumor necrosis factor receptor-associated protein 1 (TRAP1), a representative mitochondrial HSP, in a normal human hepatocyte cell line, Chang cells. DFO specifically decreased TRAP1 levels, increasing reactive oxygen species (ROS) and caveolin-1 (Cav-1), a marker protein of senescence. To examine whether these effects of DFO are reversed, we established TRAP1-overexpressing Chang cells. DFO treatment to TRAP1-overexpressing cells resulted in decreases in levels of ROS, Cav-1, glutathione peroxidase (GPX), and manganese superoxide dismutase (MnSOD) levels as well as senescence-associated beta-galactosidase (SA beta-gal) activity. These results suggest that TRAP1 might play a role in protecting mitochondria against damaging stimuli via decrease of ROS generation.

Cell Line↗

PubMed2007

Functional divergence after gene duplication and sequence-structure relationship: a case study of G-protein alpha subunits.

In this article, we use animal G-protein alpha subunit family as an example to illustrate a comprehensive analytical pipeline for detecting different types of functional divergence of protein families, which is phylogeny-dependent, combined with ancestral sequence inference and available protein structure information. In particular, we focus on (i) Type-I functional divergence, or site-specific rate shift, as typically exemplified by amino acid residue highly conserved in a subset of homologous genes but highly variable in a different subset of homologous genes, and (ii) Type-II functional divergence, or the shift of cluster-specific amino acid property, as exemplified by a radical shift of amino acid property between duplicate genes, which is otherwise evolutionally conserved. We utilized the software DIVERGE2 to carry out these analyses. In the case of G-protein alpha subunit gene family, we have predicted amino acid residues that are related to either Type-I or Type-II functional divergence. The inferred ancestral sequences for these sites are helpful to explore the trends of functional divergence. Finally, these predicted residues are mapped to the protein structures to test whether these residues may have 3D structure or solvent accessibility preference.

Amino Acid Sequence↗

PubMed2006

Inhibitory effect of Hsp70 on angiotensin II-induced vascular smooth muscle cell hypertrophy.

Angiotensin II (Ang II), which is an important mediator of both vascular responsiveness and growth, has been shown to induce vascular smooth muscle cell (VSMC) hypertrophy via the activation of a complex series of intracellular signaling events. Heat shock protein 70 (Hsp70) has recently been shown to protect against Ang II-induced hypertension. In this study, we tested the hypothesis that Hsp70 can protect VSMC from Ang II-induced hypertrophy. We treated VSMCs with Ang II to induce hypertrophy and to activate MAPK signaling pathway. We observed that the augmentation of Hsp70 expression inhibited Ang II-stimulated VSMC hypertrophy. This inhibitory effect of Hsp70 appears to be partly due to extracellular signal-regulated kinase (ERK1/2) inactivation, which in turn, may possibly result from the accumulation of MAP kinase phosphatase-1 (MKP-1).

Angiotensin II↗

PubMed2006

Comparative proteomic analysis of human leukemic cells with and without inducible expression of leukemogenic AML1-ETO protein.

AML1-ETO is a leukemogenic fusion protein generated by chromosomal translocation t(8; 21) (q22; q22), one of the most frequent chromosomal abnormalities in acute myeloid leukemia. The fusion protein has been shown to present dichotomous functions on leukemic cells: growth arrest versus differentiation block. However, their precise molecular mechanisms are not completely clear. In this work, we try to explore potential AML1-ETO-targeted proteins through comparing two-dimensional electrophoresis (2DE)-based global protein expression profiles of leukemic U937 cells with and without inducible expression of AML1-ETO. As a result, we identified 14 unique proteins deregulated in AML1-ETO-carrying leukemic cells, including 3 up-regulated such as hairy and enhancer of split 5 (HES5) and 11 down-regulated such as MAT1 (menage a trois-1) and mitogen-activated protein kinase organizer 1 (MORG1). These proteins were widely involved in stem cell maintenance, cell cycle, signal transduction and transcription. The further investigation on their roles in leukemic cells will uncover new clues to understanding leukemogenic effects of AML1-ETO fusion protein.

Cell Line, Tumor↗

PubMed2006

Vascular dynamics and BOLD fMRI: CBF level effects and analysis considerations.

Changes in the cerebral blood flow (CBF) baseline produce significant changes to the hemodynamic response. This work shows that increases in the baseline blood flow level produce blood oxygenation-level dependent (BOLD) and blood flow responses that are slower and lower in amplitude, while decreases in the baseline blood flow level produce faster and higher amplitude hemodynamic responses. This effect was characterized using a vascular model of the hemodynamic response that separated arterial blood flow response from the venous blood volume response and linked the input stimulus to the vascular response. The model predicted the baseline blood flow level effects to be dominated by changes in the arterial vasculature. Specifically, it predicted changes in the arterial blood flow time constant and venous blood volume time constant parameters of +294% and -24%, respectively, for a 27% increase in the baseline blood flow. The vascular model performance was compared to an empirical model of the hemodynamic response. The vascular and empirical hemodynamic models captured most of the baseline blood flow level effects observed and can be used to correct for these effects in fMRI data. While the empirical hemodynamic model is easy to implement, it did not incorporate any explicit physiological information.

Algorithms↗

PubMed2006

Impact of newly diagnosed breast cancer on quality of life among Chinese women.

BACKGROUND: Being diagnosed with breast cancer is a very stressful event that has a profound impact on multiple aspects of a patient's daily life. Little is known about the quality of life (QOL) of Chinese women with newly diagnosed breast cancer. METHODS: The authors evaluated QOL in 2,236 Chinese women with newly diagnosed breast cancer who were recruited into the Shanghai Breast Cancer Survival Study between April 1, 2002 and March 31, 2004. Patients' QOL was assessed after cancer diagnosis (median time 6.4 months; range 3.6-11.1 months) by using the General Quality of Life Inventory. Multiple linear regression models were used to analyze the associations of QOL outcomes with medical and socio-demographic factors. RESULTS: Patients showed significantly worse overall QOL and perceived health status than healthy women, reflected mainly by lower QOL scores in physical and psychological well-being domains. Completion of radiotherapy, ever use of tamoxifen, being underweight, having an increased number of chronic diseases, and low household income were significantly associated with lower overall QOL scores after adjusting for other factors. Age at diagnosis was inversely associated with physical well-being, positively associated with material well-being, and had minimal influence on overall QOL. Stage of disease, chemotherapy, and education were only associated with certain domains, but had no influence on overall QOL. Estrogen receptor/progesterone receptor status and type of surgery or immunotherapy did not appear to be associated with QOL. CONCLUSIONS: The findings of the present study provide important information on QOL and their correlates among Chinese women with newly diagnosed breast cancer and are helpful in developing treatment strategies accordingly.

Adaptation, Psychological↗

PubMed2006

Complementary activation of peripheral natural killer cell immunity in nasopharyngeal carcinoma.

NK cells and alphabeta- and gammadelta-CTL play important roles in cellular immunity against tumors. We previously demonstrated that NPC patients have a quantitative and qualitative deficit in gammadelta-CTL and EBV-specific alphabeta-CTL when compared to normal subjects and NPC long-term survivors. In this study we report further observations of a complementary activation of peripheral NK cells in NPC patients. The NK cells in these patients, compared to those of healthy subjects and NPC survivors, were preferentially activated in response to the stimulation of myeloma cell line XG-7 and expanded in the presence of exogenous IL-2. The production of IFN-gamma was lowest in the patient group, whereas IL-12, IL-15 and TNF-alpha were produced in higher levels in patients than in the donors and survivors. The cytolytic effect of the NK cells against NPC cells in the patient group was also higher than that of the donors and survivors. Furthermore, the patients at later stages of NPC had lower gammadelta-CTL activity but higher NK cytotoxicity towards NPC targets, with higher production of IL-12, IL-15 and TNF-alpha but lower production of IFN-gamma than in patients at earlier stages. This might be part of a triggered compensatory re-activation of the innate immunity, believed to be mediated through various cytokines and chemokines when adaptive T cell immunity is breached. Together, these data suggest complementary roles of innate and adaptive immune response in tumor immunity where NK cells, gammadelta- and alphabeta-CTL compensate for the deficits of one another at different stages of tumor invasion.

Asian People↗

PubMed2006

Leukemogenic AML1-ETO fusion protein upregulates expression of connexin 43: the role in AML 1-ETO-induced growth arrest in leukemic cells.

AML1-ETO, a fusion protein generated by the chromosomal translocation t(8;21), is frequently associated with acute myeloid leukemia (AML). In addition to blocking differentiation, AML1-ETO is also shown to induce growth arrest in AML cells, which is unfavorable for leukemogenesis harboring the t(8;21) translocation. However, its precise mechanism is still unclear. Here we provide the first demonstration that the conditional expression of AML1-ETO by the ecdysone-inducible system dramatically increases the expression of connexin 43 (CX43), together with growth arrest at G1 phase in leukemic U937 cells. We also show that the CX43 induction inhibits the proliferation of U937 cells at G1 phase, while the suppression of CX43 expression by small interfering RNA (siRNA) effectively overcomes the growth-inhibitory effect of AML1 -ETO in leukemic cells. Furthermore, either AML1-ETO or CX43 induction elevates cell-cycle negative regulator P27(kip1) protein by inhibiting its degradation, which is antagonized by siRNA against CX43. Taken together, our data indicate that CX43 plays a role in AML1-ETO-induced growth arrest possibly through the accumulation of P27(kip1) protein. The potential mutation or/and epigenetic alterations of CX43 and its related gene(s) deserve to be explored in AML1-ETO-positive AML patients.

Base Sequence↗

PubMed2006

Differential protein expression in hypertrophic heart with and without hypertension in spontaneously hypertensive rats.

Although cardiac hypertrophy in hypertension has been well recognized, the molecular mechanisms for the development of hypertrophy are still largely unknown. In this study, the protein expression profiles of left ventricular myocardia in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at different ages were analyzed using 2-DE in combination with MALDI-TOF/TOF MS/MS. The results showed that 20 proteins were modulated in the hypertrophic myocardium. Out of these modulated proteins, 13 proteins presented significant changes in SHR at an early stage prior to the development of sustained hypertension, while the changes of the other 7 protein expressions occurred only at a late stage in SHR when the blood pressure was significantly elevated, and were largely reversible by treatment with rennin-angiotensin-aldosterone system inhibitors losartan or enalapril. These data demonstrate that the changes in energy metabolism in the hypertrophied heart favor an increase in glycolysis and a decrease in oxidation of fatty acid and glucose, which occur at an early stage in SHR without hypertension. Our results also provide evidence to support the hypothesis that oxidative stress plays an important role in the development of hypertensive cardiac hypertrophy.

Age Factors↗

PubMed2006

Comparative proteomic analysis of hypoxia-treated and untreated human leukemic U937 cells.

We reported recently that moderate hypoxia and hypoxia-mimetic agents could induce growth arrest and differentiation of leukemic cells via the mediation of hypoxia-inducible factor 1 alpha (HIF-1alpha), but the exact molecular mechanisms remain largely unknown. In this study, human acute promonocytic leukemic U937 cells were incubated under 2% O2 or in 50 microM of the hypoxia mimetic agent cobalt chloride (CoCl2) and normal oxygen for 24 h, and their protein expression profiles were compared by 2-DE coupled with MALDI-TOF/TOF MS/MS. We identified 62 and 16 proteins that were significantly deregulated by hypoxia and CoCl2 treatment, respectively. These proteins were mainly involved in metabolism, gene expression regulation, signal transduction, cell proliferation, differentiation and apoptosis. As an example, N-myc downstream regulated gene 1 (NDRG1), a putative differentiation-related gene, was up-regulated in both 2% O2- and CoCl2-treated U937 cells. Moreover, enforced HIF-1alpha expression also elevated NDRG1 mRNA and protein in U937 cells. These data will provide some clues for understanding mechanisms by which leukemic cells response to hypoxia.

Apoptosis↗

PubMed2006

Preparation, characterization, and pharmacokinetics of sterically stabilized nimodipine-containing liposomes.

Nimodipine is a dihydropyridine calcium antagonist used in clinical trials in the treatment of ischemic damage in subarachnoid hemorrhage and commercially available as nimotop intravenous infusion solution and tablets. However, due to its poor solubility in water, intravenous administration depends on the use of the dehydrated alcohol to achieve a clinically relevant concentrated infusion solution while the low bioavailability of the nimotop tablets were far away from content. We have prepared a well-characterized novel lyophilized liposome-based nimodipine formulation that is sterile and easy-to-use. Of the several formulations examined, nimodipine-liposomes composed of ePC/CHOL 20:3 and co-surfactant poloxamer 188/sodium deoxycholate/ePC/3:0.3:5 were chosen for further studies. This composition was found to give more stable liposomes than other formulations. It gave 89.9% entrapment efficiency and particle size of 200 nm after lyophilization. The pharmacokinetic parameters following orally and intravenously administration to New Zealand rabbits were determined and compared with those of commercial nimodipine formulations. Encapsulation of nimodipine in liposomes produced marked differences over those of commercial preparations with an increased C(max), prolonged elimination half-life, and an increased value for AUC. The obtained values for mean residence time (MRT) indicated that nimodipine remains longer for liposomal formulation. Thus an optimum i.v. liposome formulation for nimodipine can be developed for an alternative to the commercial nimodipine preparations.

Animals↗

PubMed2006

Takagi-Sugeno fuzzy-model-based fault detection for networked control systems with Markov delays.

A Takagi-Sugeno (T-S) model is employed to represent a networked control system (NCS) with different network-induced delays. Comparing with existing NCS modeling methods, this approach does not require the knowledge of exact values of network-induced delays. Instead, it addresses situations involving all possible network-induced delays. Moreover, this approach also handles data-packet loss. As an application of the T-S-based modeling method, a parity-equation approach and a fuzzy-observer-based approach for fault detection of an NCS were developed. An example of a two-link inverted pendulum is used to illustrate the utility and viability of the proposed approaches.

Algorithms↗

PubMed2006

[Detection of physical status of human papillomavirus 16 in cervical cancer tissue and SiHa cell line by multiplex real-time polymerase chain reaction].

BACKGROUND & OBJECTIVE: The integration of high-risk human papillomavirus (HPV) into host cell genome is one of the major contributing factors to cervical malignant transformation. The detection of HPV integration is helpful for understanding its role in cervical carcinogenesis and tumor progression. However, there is no ideal detection method of HPV physical status for clinical use. The study was to explore an ideal method of detecting the physical status of HPV-16. METHODS: Setting HPV-16 plasmid as standard, multiplex real-time polymerase chain reaction (PCR) using 2 different fluorescent report radicals was used to quantify the copy numbers of E2 and E6 genes for analysis of the physical status of HPV-16 according to E2/E6. Multiplex real-time PCR test and Southern blot results of cervical cancer cell line SiHa and 27 specimens of HPV-16-positive cervical squamous cell carcinoma were compared. RESULTS: There was a linear relationship between the threshold cycle values and the copy numbers of E2 and E6 in both standard curves, with the correlation coefficients of 1.00 and the amplification efficiencies of above 95%. The 95% reference range of plasmid E2/E6 ratio, in which the amount of E2 DNA was equal to that of E6 DNA, was 0.81-1.29. The cut-off value of E2/E6, which was used to distinguish the pure episomal form from a mixed form of episomal and integrated HPV-16, was 0.81 in the multiplex real-time PCR test. HPV-16 was observed to be integrated into the host genome of SiHa cells by multiplex real-time PCR and Southern blot. The coincidence rate of multiplex real-time PCR and Southern blot was 81.5% (22/27) in the cervical squamous cell cancer tissues (kappa=0.844, P<0.001). CONCLUSION: Multiplex real-time PCR test is a rapid, sensitive and reliable method for detecting the physical status of HPV-16 DNA, and is convenient to be applied in paraffin-embedded tissue and small preneoplastic or early neoplastic cervical lesions, even in cervical scrapes which contain a small amount of DNA.

Adult↗

PubMed2006

[Determination of 20 (S)-ginsengnoside Rh2 in the alkali-hydrolysis product of saponins from leaves of Panax qinquefolium by RP-HPLC].

OBJECTIVE: To determine 20(S)-ginsengnoside Rh2 in the hydrolysis product of saponins from leaves of Panax qinquefolium. METHOD: The separation was performed on ZORBAX EXEND C18 column (4.6 mm x 250 mm, 5 microm), eluted with methanol and water (85:15) as mobile phase with the rate of 1.2 mL x min(-1) at 25 degrees C, the wavelength for measurement was 203 nm. RESULT: The calibration curve was linear in the range of 0.5-25 microg for 20(S)-ginsengnoside Rh2(r = 0.9999, n = 7). The average recovery was 99.7% (RSD= 1.0%). CONCLUSION: This method is simple, accurate, reliable and reproducible. The result shows that the transform ratio of 20(S)-ginsengnoside Rh2 is high by this hydrolysis method.

Chromatography, High Pressure Liquid↗

PubMed2006

[Reversal of multi-drug resistance in ovarian cancer cell by RNA interference].

OBJECTIVE: To investigate the effects of small interference RNA (siRNA) on the inhibition of MDR1 mRNA and P-gp expression of ovarian cancer cells with high expression of MDR1 gene, and reversal of drug resistance. METHODS: siRNA was synthesized and transfected into human ovarian cancer cell line OVCAR8/TR by liposome. The expression of MDR1 mRNA at different times after transfection was measured by real time RT-PCR and the P-gp expression was detected by flow cytometry. Adenosine triphosphate (ATP)-bioluminence assay was applied to check the drug sensitivity to four different chemotherapeutic agents before and after transfection. RESULTS: The suppression rates of MDR1 mRNA were 26.42%, 84.00%, 78.43%, 45.85% and 0 respectively at 24, 48, 72, 96 and 120 hours after transfection. The P-gp suppression rates were 16.71%, 49.64%, 85.23%, 65.98%, 9.44% respectively at 24, 48, 72, 96 and 120 hours after transfection. The maximal suppression rates of MDR1 mRNA and P-gp occurred at 48 and 72 hours after transfection respectively. ATP-bioluminence assay showed that OVCAR8/TR cells were sensitive to fluorouracil, resistant to cisplatin, doxorubicin (adriamycin) and paclitaxel (taxol). After siRNA treatment, OVCAR8/TR cells were sensitive to paclitaxel and doxorubicin, but the resistance to cisplatin could not be reversed. CONCLUSIONS: RNA interference (RNAi) presents in human ovarian cancer cells. siRNA can effectively inhibit the expression of mRNA and P-gp of the multidrug resistance gene MDR1, and can reverse the drug resistance to chemotherapeutic agents which are transferred by P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Cloning and characterization of a novel sperm tail protein, NYD-SP28.

In this study, a gene coding a novel human sperm tail protein named NYD-SP28 was cloned and characterized using a complementary DNA (cDNA) microarray. Its expression was 3.5 times higher in human testis than in fetal testis, and very high in human spermatozoa. The full length of NYD-SP28 cDNA was 1798 bp and encoded a 484-amino-acid protein. Motif analysis revealed that the protein contained a cluster of phosphorylation sites, N-glycosylation sites and N-myristoylation sites. Immunohistochemical analysis of normal human testes showed that NYD-SP28 was expressed in the cytoplasm of spermatogenic cells but not in interstitial cells. The EGFP-NYD-SP28 fusion protein was also localized in the cytoplasm of transfected 7721 cells. In human spermatozoa, NYD-SP28 immunoreactivity was detected in entire sperm tail. Using the two-dimensional (2-D) gel electrophoresis and immunoblotting technique, NYD-SP28 was found to be post-translationally modified during sperm capacitation. In conclusion, these results suggest that NYD-SP28 is a new human sperm tail protein and might play an important role during sperm capacitation.

Adult↗

PubMed2005

Lack of effect of beta-cyclodextrin and its water-soluble derivatives on in vitro drug transport across rat intestinal epithelium.

The present study aimed to investigate whether beta-cyclodetxrin (beta-CD) and its water-soluble derivatives, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sulfobutyl ether beta-cyclodextrin (SBE-beta-CD), exert any effects on the permeation of two drug transport markers (propranolol and lucifer yellow) across rat intestinal epithelium. Rat ileum was stripped of its serosa and mounted inside an Ussing Chamber. Apparent permeability coefficients (P(app)) of the markers from the mucosal to serosal side of the tissue were determined at 37 degrees C in the presence and absence of the beta-cyclodextrins on the mucosal side. Potential difference (PD) was constantly monitored during each experiment to ensure maintenance of the viability and integrity of the tissue. Pre-incubation with 1% beta-CD, 1% HP-beta-CD or 1.48% SBE-beta-CD on the mucosal side for 30 min did not significantly alter the PD and the propranolol permeability (p>0.05). Co-incubation with 1% beta-CD or 1% HP-beta-CD exerted no significant effect on the P(app) of both propranolol and lucifer yellow (p>0.05), but co-incubation with 1.48% SBE-beta-CD lowered the P(app) of propranolol from (1.71+/-0.44)x10(-5) to (0.19+/-0.04)x10(-5)cm/s, which may be ascribed to the molecular complexation of propranolol with SBE-beta-CD. All three beta-cyclodextrins exert no apparent impact on both (passive) transcellar and paracellular drug transports.

Adrenergic beta-Antagonists↗