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Biomedical subjects

Ye Sun

Publications and source records attributed to Ye Sun.

At least 19 recordsLinked to original sources

Reframing the asthma microbiome: Multikingdom, multisite, and multiomic perspectives.

The field of asthma microbiome research has shifted rapidly in recent years. Advances in sequencing technology have led to an increased ability to characterize multikingdom microbial species and integration with host -omics profiling to enhance future translational applications. Traditional bacteria-centric, cross-sectional studies are giving way to mechanistic frameworks that incorporate fungi, viruses, and host-immune interactions. In this state-of-the-art review of emerging concepts in microbiome asthma research, we first propose a structured framework to consider microbiome studies across 5 major domains-microbial kingdom, site of sampling, integration with host -omics, clinical outcome domain, and translational relevance-in order to synthesize recent high-impact human microbiome studies in asthma. We highlight emerging evidence that fungal and viral communities contribute independently to asthma risk and that human microbial communities are linked to distinct inflammatory and immune pathways shaped by host genetic susceptibility.

Asthma↗

Integrative multi-omics analysis unravels the metabolic landscape and reveals serum biomarkers for early diagnosis of hyperuricemia.

BACKGROUND: Hyperuricemia (HUA) is a major risk factor for gout and multiple metabolic disorders. Although serum uric acid (UA) is the gold standard for HUA diagnosis, it fails to reflect early metabolic disturbances and shows limited predictive value for asymptomatic HUA. This study sought to elucidate the pathological mechanisms underlying HUA and identify novel diagnostic biomarkers beyond UA. METHODS: This study enrolled 195 patients with HUA and 98 healthy controls. Global metabolomics and proteomics profiling were performed to characterize molecular alterations underlying HUA. Based on the biological relevance of the shared dysregulated pathways, a pathway correlation network was constructed to elucidate the pathological mechanisms driving HUA initiation and progression. Furthermore, diagnostic biomarkers for HUA were identified using machine learning algorithms, and were validated with an external cohort. RESULTS: HUA patients exhibited distinct metabolic and proteomic profiles compared with healthy controls. Integrated multi-omics pathway analysis revealed that peroxisome proliferators-activated receptor signaling pathway, arachidonic acid metabolism, purine metabolism, pyrimidine metabolism and sphingolipid signaling pathway were significantly dysregulated in HUA. Among them, arachidonic acid metabolism was identified as a hub pathway involved in HUA progression. Furthermore, a metabolite panel consisting of cysteine-S-sulfate, glycerophosphocholine and 4-hydroxyphenylpyruvic acid was screened by machine learning and validated in an independent cohort, which showed slightly higher diagnostic performance for HUA than UA. CONCLUSIONS: This study reveals the core metabolic and protein regulatory networks of HUA, and identifies a novel serum metabolite panel for the diagnosis of HUA. These findings provide new insights for improved clinical diagnosis and management.

Humans↗

Molecular authentication of Radix Puerariae Lobatae and Radix Puerariae Thomsonii by ITS and 5S rRNA spacer sequencing.

In the present study, we examined nuclear DNA sequences in an attempt to reveal the relationships between Pueraria lobata (Willd). Ohwi, P. thomsonii Benth., and P. montana (Lour.) Merr. We found that internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA are highly divergent in P. lobata and P. thomsonii, and four types of ITS with different length are found in the two species. On the other hand, DNA sequences of 5S rRNA gene spacer are highly conserved across multiple copies in P. lobata and P. thomsonii, they could be used to identify P. lobata, P. thomsonii, and P. montana of this complex, and may serve as a useful tool in medical authentication of Radix Puerariae Lobatae and Radix Puerariae Thomsonii.

DNA, Plant↗

Label-free detection of biomolecules on microarrays using surface-colloid interaction.

Binding of charged nanoparticles to nonmodified DNA and RNA target molecules on microarrays allows detection of these nucleic acids by locating bound nanoparticles on microarray surface. Two computational models have been developed to study the ionic interaction of colloidal particles and biopolymer molecules on a microarray surface. One model represents a basic approach based on mass action law for simulation charge effects versus the chemical composition of the interacting array surface and nanoparticle. The second model is implementation of the advanced Gouy-Chapman-Stern-Graham model for describing effects on liquid-solid interface. We found that both models predict selective binding of colloidal particles to large target molecules on the surface with no binding to smaller capture molecules. This binding regime is considered to be very beneficial for application of charged nanoparticles for detection of nonmodified DNA and RNA target molecules on microarrays. The theoretical considerations are in qualitative agreement with the experimental results for detecting large target DNA and a 50-base long synthetic oligonucleotide on the amino-modified microarray substrate. The experimental and theoretical results of this study allow further development of the label-free microarray technology demonstrated previously for gene expression analysis that is free of reverse transcription and dye labeling.

Colloids↗

Expression and characterization of Acidothermus cellulolyticus E1 endoglucanase in transgenic duckweed Lemna minor 8627.

Endoglucanase E1 from Acidothermus cellulolyticus was expressed cytosolically under control of the cauliflower mosaic virus 35S promoter in transgenic duckweed, Lemna minor 8627 without any obvious observable phenotypic effects on morphology or rate of growth. The recombinant enzyme co-migrated with the purified catalytic domain fraction of the native E1 protein on western blot analysis, revealing that the cellulose-binding domain was cleaved near or in the linker region. The duckweed-expressed enzyme was biologically active and the expression level was up to 0.24% of total soluble protein. The endoglucanase activity with carboxymethylcellulose averaged 0.2 units mg protein(-1) extracted from fresh duckweed. The optimal temperature and pH for E1 enzyme activity were about 80 degrees C and pH 5, respectively. While extraction with HEPES (N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]) buffer (pH 8) resulted in the highest recovery of total soluble proteins and E1 enzyme, extraction with citrate buffer (pH 4.8) at 65 degrees C enriched relative amounts of E1 enzyme in the extract. This study demonstrates that duckweed may offer new options for the expression of cellulolytic enzymes in transgenic plants.

Buffers↗

Mechanism of ZnO nanotube growth by hydrothermal methods on ZnO film-coated Si substrates.

ZnO nanorods (NRs) and nanotubes (NTs) have been synthesized by a hydrothermal method on Si substrates that had been precoated (by pulsed laser deposition (PLD)) with a thin ZnO film. High-resolution transmission electron microscopy and selected area electron diffraction analysis confirm that the NTs are ZnO single crystals and that their growth direction is along [0001] (the c-axis). Scanning electron microscopy points to the early-time formation of two classes of NRs on the PLD ZnO coating, one of which is longer and displays higher length/diameter aspect ratios than the other. The morphologies of NRs belonging to the first of these classes were seen to evolve with time, progressively tapering, and producing volcano-like surface structures that develop into NTs. In contrast, NRs belonging to the other (shorter) class retain their hexagonal cross-section and have flat tops. To explain these emergent structures and, in particular, the selective growth of ZnO NTs, we have undertaken a systematic investigation of the effects of different substrates (e.g., borosilicate glass, Pt-coated glass, and both bare and PLD ZnO-coated Si wafers) and of the reactive solution on the growth properties of ZnO NRs, NTs, and the ZnO nanopowders that precipitate from the reactive mixture. The experimental findings suggest the following ZnO NT growth mechanism. The PLD ZnO film consists of many nanocrystallites, with a preferred c-axis alignment. These serve to nucleate the hydrothermal growth of (c-axis aligned) NRs. The NRs are deduced to be Zn-polar, but can be either Zn-atom or O-atom terminated. It is proposed that the different surface terminations influence (by electrostatic interactions) the cation (Zn(2+) and ZnOH(+)) to anion (OH(-)) concentration ratio in the double layer at the growing polar surface. Zn-atom termination causes a reduction in the local Zn(2+)/OH(-) (and ZnOH(+)/OH(-)) ratios (i.e., the extent of solution supersaturation) relative to those in the bulk solution, thereby encouraging tapered NR growth and, as the zinc concentration falls further, the emergence of volcano-like structures on the polar surface, which seed the subsequent growth of ZnO NTs.

Journal Article↗

Single chain antibody displays glutathione S-transferase activity.

Substrate binding and the subsequent reaction are the two principal phenomena that underlie the activity of enzymes, and many enzyme-like catalysts were generated based on the phenomena. The single chain variable region fragment of antibody 2F3 (scFv2F3) was elicited against hapten GSH-S-DN2phBu, a conjugate of glutathione (GSH), butyl alcohol, and 1-chloro-2,4-dinitrobenzene (CDNB); it can therefore bind both GSH and CDNB, the substrates of native glutathione S-transferases (GSTs). It was shown previously that there is a serine residue that is the catalytic group of GST in the CDR regions of scFv2F3 close to the sulfhydryl of GSH. Thus, we anticipated that scFv2F3 will display GST activity. The experimental results showed that scFv2F3 indeed displayed GST activity that is equivalent to the rat-class GST T-2-2 and exhibited pH- and temperature-dependent catalytic activity. Steady-state kinetic studies showed that the Km values for the substrates are close to those of native GSTs, indicating that scFv2F3 has strong affinities for the substrates. Compared with some other GSTs, its kcat value was found to be low, which could be caused by the similarity between the GSH-S-DN2phBu and the reaction product of GSH and CDNB. These results showed that our approach to imitating enzymes is correct, which is that an active site may catalyze a chemical reaction when a catalytic group locates beside a substrate-binding site of a receptor. It is important to consider product inhibition in hapten design in order to obtain a mimic with a high catalytic efficiency.

Amino Acid Sequence↗

Microarray gene expression analysis free of reverse transcription and dye labeling.

A new microarray system has been developed for gene expression analysis using cationic gold nanoparticles with diameters of 250 nm as a target detection reagent. The approach utilizes nonlabeled target molecules hybridizing with complementary probes on the array, followed by incubation in a colloidal gold solution. The hybridization signal results from the precipitation of nanogold particles on the hybridized spots due to the electrostatic attraction of the cationic gold particles and the anionic phosphate groups in the target DNA backbone. In contrast to conventional fluorescent detection, this nanoparticle-based detection system eliminates the target labeling procedure. The visualization of hybridization signals can be accomplished with a flatbed scanner instead of a confocal laser scanner, which greatly simplifies the process and reduces the cost. The sensitivity is estimated to be less than 2 pg of DNA molecules captured on the array surface. The signal from hybridized spots quantitatively represents the amount of captured target DNA and therefore permits quantitative gene expression analysis. Cross-array reproducibility is adequate for detecting twofold or less signal changes across two microarray experiments.

Bacteriophages↗

Dilute acid pretreatment of rye straw and bermudagrass for ethanol production.

Ethanol production from lignocellulosic materials provides an alternative energy production system. Rye and bermudagrass that are used in hog farms for nutrient uptake from swine wastewater have the potential for fuel ethanol production because they have a relative high cellulose and hemicellulose content. Dilute sulfuric acid pretreatment of rye straw and bermudagrass before enzymatic hydrolysis of cellulose was investigated in this study. The biomass at a solid loading rate of 10% was pretreated at 121 degrees C with different sulfuric acid concentrations (0.6, 0.9, 1.2 and 1.5%, w/w) and residence times (30, 60, and 90 min). Total reducing sugars, arabinose, galactose, glucose, and xylose in the prehydrolyzate were analyzed. In addition, the solid residues were hydrolyzed by cellulases to investigate the enzymatic digestibility. With the increasing acid concentration and residence time, the amount of arabinose and galactose in the filtrates increased. The glucose concentration in the prehydrolyzate of rye straw was not significantly influenced by the sulfuric acid concentration and residence time, but it increased in the prehydrolyzate of bermudagrass with the increase of pretreatment severity. The xylose concentration in the filtrates increased with the increase of sulfuric acid concentration and residence time. Most of the arabinan, galactan and xylan in the biomass were hydrolyzed during the acid pretreatment. Cellulose remaining in the pretreated feedstock was highly digestible by cellulases from Trichoderma reesei.

Bioelectric Energy Sources↗

Phylogenetic analysis of Bambusa (Poaceae: Bambusoideae) based on internal transcribed spacer sequences of nuclear ribosomal DNA.

Phylogenetic analyses of Bambusa species were performed using internal transcribed spacer sequences of nuclear ribosomal DNA. The 21 species sampled included members of Bambusa (sensu stricto), Dendrocalamopsis, Dendrocalamus, Guadua, Leleba, and Lingnania. Arundinaria gigantea was used as an outgroup. Using the maximum parsimony method with PAUP*, gaps were treated as missing states or new states. Parsimonious analysis revealed that Dendrocalamus latiflorus was closely related to the members of Dendrocalamopsis. Dendrocalamus membranaceus was a sister species to Dendrocalamus strictus. Three Dendrocalamus species were closely related to and nested in a polyphyletic Bambusa. Bambusa subaequalis was a sister species to B. multiplex, B. emeiensis to B. chungii, B. contracta to B. hainanensis, and B. flexuosa was a sister species to B. sinospinosa, B. tuldoides, B. surrecta, B. intermedia, and B. valida group, which raised doubts about the monophyly of the subgenera Bambusa (sensu stricto), Dendrocalamopsis, Leleba, and Lingnania under the genus Bambusa.

Bambusa↗

Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics.

Epidermal growth factor receptor (ErbB1, EGFR) is overexpressed in a variety of human cancer cells. It has been considered as a rational target for drug delivery. To identify novel ligands with specific binding capabilities to EGFR, we screened a phage display peptide library and found an enriched phage clone encoding the amino acid sequence YHWYGYTPQNVI (designated as GE11). Competitive binding assay and Scatchard analysis revealed that GE11 peptide bound specifically and efficiently to EGFR with a dissociation constant of approximately 22 nM, but with much lower mitogenic activity than with EGF. We showed that the peptides were internalized preferentially into EGFR highly expressing cells, and they accumulated in EGFR overexpressing tumor xenografts after i.v. delivery in vivo. In gene delivery studies, GE11-conjugated polyethylenimine (PEI) vectors were less mitogenic, but still quite efficient at transfecting genes into EGFR highly expressing cells and tumor xenografts. Taken together, GE11 is a potentially safe and efficient targeting moiety for selective drug delivery systems mediated through EGFR.

Cell Line, Tumor↗

[Effect of sijunzi decoction on malondialdehyde content and telomerase activity in heart, liver and brain tissues of D-galactose induced aging model mice].

OBJECTIVE: To investigate the effect of Sijunzi decoction (SJZD) on malondialdehyde (MDA) content and telomerase activity in heart, liver and brain tissues of D-galactose (D-gal) induced aging model mice. METHODS: D-gal aging mice model was established by cervicodorsal region subcutaneous injection with 10% D-gal once a day for six successive months. The model mice in the low-, middle- and high-dose SJZD treated groups were treated with SJZD in a dose of 6 g/kg, 12 g/kg, 24 g/kg per day respectively in the volume of 0.2 ml/10 g for 6 successive weeks. While the mice in the normal control group (NCG, non-modeled) and the model control group (MCG, modeled but untreated) were treated with distilled water instead. The MDA content and telomerase activity in heart, liver and brain tissues of mice was measured with TBA colorimetric method and PCR-ELISA respectively. RESULTS: In MCG, the MDA content in heart, liver and brain tissues was significantly higher (P < 0.01), and the telomerase activity in liver and heart tissues was significantly lower (P < 0.01) but that in brain tissue was insignificant different to that in NCG (P > 0.05) respectively. As compared with MCG, the MDA content was significantly lower in the three SJZD treated group (P < 0.01). In comparison of telomerase activity between MCG and SJZD treated groups, it was shown that in heart tissue, there was an increased trend of the activity in the low-dose and middle-dose group, but with statistical insignificance (P > 0.05), but it did show a significant increase in the high-dose group (P < 0.05); in liver tissue no significant difference was shown between the three SJZD treated groups and MCG (P > 0.05); as for that in brain tissue, significant increase only shown in the high-dose group (P < 0.01). CONCLUSION: SJZD can antagonize free radical injury, decrease the MDA content of heart, liver and brain in D-gal aging mice, and increase the telomerase activity in heart and brain tissues but with no effect on that in liver tissue.

Aging↗

The molecular mechanism of protecting cells against oxidative stress by 2-selenium-bridged beta-cyclodextrin with glutathione peroxidase activity.

Ultraviolet B (UVB) induces apoptosis and lipid peroxidation of NIH3T3 cells by producing reactive oxygen species (ROS). Glutathione peroxidase (GPX) is one of the most important antioxidant enzymes in organism and it can scavenge ROS. 2-selenium-bridged beta-cyclodextrin (2-SeCD) is a GPX mimic generated in our lab. Its GPX activity is 7.4 U/mumol, which is 7.5 times as much as that of ebselen. In this paper, we have established a cell damage system using UVB radiation. Using this system, we have determined antioxidant effect of 2-SeCD by comparison of malondialdehyde (MDA) and H(2)O(2) contents in NIH3T3 cells before and after UVB radiation. Experimental results indicate that 2-SeCD can inhibit lipid peroxidation and protect the cells from the damage generated by UVB radiation. To evaluate the molecular mechanism of this protection, we determined the effect of 2-SeCD on the expression of p53 and Bcl-2 in NIH3T3 cells. The results showed that 2-SeCD inhibits the increase of p53 expression level and the decrease of expression of Bcl-2 induced by UVB radiation. Thus, we have concluded that protection of NIH3T3 cells against oxidative stress by 2-SeCD was carried out by regulation of the expression of Bcl-2 and p53.

Animals↗

Selenium-containing 15-mer peptides with high glutathione peroxidase-like activity.

Glutathione peroxidase (GPX) is one of the most crucial antioxidant enzymes in a variety of organisms. Here we described a new strategy for generating a novel GPX mimic by combination of a phage-displayed random 15-mer peptide library followed by computer-aided rational design and chemical mutation. The novel GPX mimic is a homodimer consisting of a 15-mer selenopeptide with an appropriate catalytic center, a specific binding site for substrates, and high catalytic efficiency. Its steady state kinetics was also studied, and the values of k(cat)/K(m)(GSH) and k(cat)/ K(mH(2)O(2)) were found to be similar to that of native GPX and the highest among the existing GPX mimics. Moreover, the novel GPX mimic was confirmed to have a strong antioxidant ability to inhibit lipid peroxidation by measuring the content of malondialdehyde, cell viability, and lactate dehydrogenase activity. Importantly, the novel GPX mimic can penetrate into the cell membrane because of its small molecular size. These characteristics endue the novel mimic with potential perspective for pharmaceutical applications.

Amino Acid Sequence↗

A novel small peptide as a targeting ligand for receptor tyrosine kinase Tie2.

Tie2 is an endothelium-specific receptor tyrosine kinase known to play an important role in tumor angiogenesis. We sought to identify a small peptide ligand against Tie2 for developing a delivery targeting agent. We used hydrophobic analysis and comparative sequence/structure analysis to select a minimal peptide based on angiopoietin-2 amino acid sequence. The resulting peptide named GA3(WTIIQRREDGSVDFQRTWKEYK) was synthesized and labeled with iodine-125 at the C-terminal tyrosine residue to characterize its binding capability. In in vitro binding assays, GA3 can not only specifically bind to SMMC7721-Tie2 but also compete with angiopoietin-2 in binding. Via mouse tail vein injection, 125I-labeled GA3 was found to favorably accumulate in SPC-A1 xenograft tumor tissues which positively express Tie2. These results demonstrated that GA3 may be useful as a drug or gene delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy.

Amino Acid Sequence↗

Characterization of medicinal Epimedium species by 5S rRNA gene spacer sequencing.

Sequences of 5S rRNA gene spacer were used to identify Epimedium brevicornu Maxim., E. sagittatum (Sieb. et Zucc.) Maxim., E. wushanense T. S. Ying, E. pubescens Maxim., and E. koreanum Nakai. These species are listed as source plants of Chinese medicine 'Ying Yang Huo' in the Chinese Pharmacopoeia. The neighbor-joining method was used in a sequence analysis of Epimedium species. A position-specific nucleotide was found in the 5S rRNA gene spacer for E. pubescens, E. wushanense, and E. brevicornu. A 19-bp deletion was found for E. koreanum in the 5S rRNA gene spacer. E. koreanum was most divergent from the other four endemic Chinese species of Epimedium.

DNA, Plant↗

[Relationship between the data from MR-diffusion tensor imaging and the clinical cognitive evaluation in Alzheimer's disease].

OBJECTIVE: To determine the relationship between the extent of the damage and clinical data in Alzheimer's disease (AD). METHODS: Twenty-two patients with AD and twenty-two controls received MR-diffusion tensor scanning. The fractional anisotropy (FA) values of white matter in AD patients were measured respectively in parietal lobe and the genu of corpus callosum. Independent-samples t-test for non-paired data was used to test differences between AD and controls for FA values. Correlation analysis was applied to reveal the correlations between FA values in each region and the MMSE, FOM, RVR, BD and DS scores. RESULTS: Positive correlations were found between FA values in left parietal lobe and FOM/DS, and between FA values in genu of corpus callosum and MMSE scores. CONCLUSIONS: In AD, the MR-DTI can reflect the relationship between the degree of white matter abnormalities and the cognitive impairment.

Aged↗