Biomedical subjects

Qing Zhao

Publications and source records attributed to Qing Zhao.

At least 19 recordsLinked to original sources

PubMed2026

Identification and Catalytic Optimization of Pinene Oxidases in Paeoniflorin Biosynthetic Pathway.

Paeoniflorin is a pharmacologically important cage-like monoterpene glycoside characteristic of Paeonia plants, yet its biosynthetic pathway has remained largely unresolved, hindering sustainable production. Here, we confirmed that paeoniflorin biosynthesis originates from α-pinene and identified three novel cytochrome P450 enzymes that catalyze pinene oxidation. CYP71AN126 catalyzes the hydroxylation of α-pinene at positions C4 and C10, followed by further oxidation of the alcohol to a ketone at C4, whereas CYP76A225/226 exclusively catalyze C10 hydroxylation. Virus-induced gene silencing (VIGS) assays demonstrated that silencing CYP71AN126, but not CYP76A225 and CYP76A226, significantly reduced the paeoniflorin content, indicating that C4 hydroxylation plays an important role in paeoniflorin biosynthesis, whereas C10 hydroxylation is not. Through the analysis of natural sequence and activity divergence among CYP71AN126 and CYP76A225/226, combined with protein structure prediction and site-directed mutagenesis, we identified L493 as a critical residue involved in regulating catalytic site specificity and substrate specificity of CYP71AN126. Mutation of L493 reduced or eliminated the formation of undesired C10 hydroxylation side-product and enhanced substrate specificity. These findings establish C4 oxidation of α-pinene as the critical committed step in paeoniflorin biosynthesis. Our study lays a foundation for elucidating the complete biosynthetic pathway of paeoniflorin in Paeonia and provides a target for enzyme engineering of CYP71AN126 aimed at the efficient production of paeoniflorin via synthetic biology approaches.

Paeonia genus↗

PubMed2026

In silico analysis based on network pharmacology and biomolecular informatics to explore the mechanism of action of Erjing Pills (from Shengji Zonglu) in the treatment of leukotrichia.

This study aimed to explore the core active ingredients and potential molecular mechanisms of Erjing Pills, a prescription in the classic work of Traditional Chinese Medicine, "Shengji Zonglu," in the treatment of leukotrichia by utilizing network pharmacology and biomolecular docking techniques. The chemical components and potential targets of Chinese herbal medicines were analyzed through databases such as the Traditional Chinese Medicine Systems Pharmacology Database. The targets related to leukotrichia were collected using GeneCards. The intersection targets were obtained using RStudio. The protein-protein interaction (PPI) network map and the "drug-component-target-disease" visualization network were generated using Cytoscape and STRING to screen the core components and key targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were carried out using the Database for Annotation, Visualization and Integrated Discovery and RStudio. Finally, molecular docking verification was performed by AutoDock and PyMOL (Schrödinger LLC). The key active ingredients of Erjing Pills in the treatment of leukotrichia are β-sitosterol, quercetin, baicalein, and stigmasterol. The top 5 PPI core target proteins, in order, are AKT serine/threonine kinase 1, interleukin 6, tumor protein p53, cysteine-aspartic acid protease 3, and interleukin 1 beta. The Gene Ontology enrichment analysis suggests that the biological processes mainly include responses to exogenous stimuli, membrane rafts, and DNA-binding transcription factor binding. The Kyoto Encyclopedia of Genes and Genomes pathways involve signal pathways such as lipid and atherosclerosis, hepatitis B, Kaposi sarcoma virus infection, chemical carcinogenesis, and human cytomegalovirus infection. The molecular docking results indicate that most of the main active ingredients in Erjing Pills have relatively stable binding activities with the key targets, such as AKT serine/threonine kinase 1, interleukin 6, tumor protein p53, cysteine-aspartic acid protease 3, and interleukin 1 beta, in the PPI network. The active ingredients of Erjing Pills may interfere with the pathological process of leukotrichia by regulating key targets and signal pathways. This study provides a theoretical basis for the clinical application of Erjing Pills and indicates the direction for subsequent experimental research.

Drugs, Chinese Herbal↗

PubMed2025

The chloroplast 16S rRNA dimethyltransferase BrPFC1 is required for Brassica rapa development under chilling stress.

Chloroplast ribosomal RNA (Ch-rRNA) methylation is critical for plant development and response to low temperatures. Several Ch-rRNA methyltransferases and their catalytic modes, as well as biological relevance, have been reported in model plant species. However, Ch-rRNA methyltransferases and their functional significance remain poorly characterized in crops, including leafy vegetables such as Chinese cabbage. In this study, we screened an EMS-mutagenized Chinese cabbage population and identified a yellow inner leaf (yif) mutant. This mutant develops yellowing inner leaves with reduced chlorophyll accumulation and ultrastructure-impaired chloroplasts under low-temperature conditions. Genetic analysis revealed a premature termination mutation in BrPFC1, encoding the chloroplast-localized 16S rRNA dimethyltransferase. The BrPFC1 mutation (yif) disrupts the dimethylation of 16S rRNA. The cold-sensitive phenotype of the yif mutant can be explained by temperature-dependent defects in the maturation and assembly of chloroplast ribosomes at 4°C. Through integrated analysis of chloroplast and nuclear transcriptomes coupled with translational profiling at 25°C and 4°C, we established that low temperature preferentially upregulates transcripts encoding nuclear-derived ribosomal proteins, while defective 16S rRNA specifically compromises the translational efficiency of chloroplast-encoded photosynthetic complex and ribosomal protein at 4°C. These findings establish rRNA modification by BrPFC1 as a critical regulatory layer for optimizing chloroplast translational efficiency at 4°C, providing mechanistic insights into post-translational adaptation strategies in Chinese cabbage.

Chloroplasts↗

PubMed2006

Structural requirements for optimized delivery, inhibition of oxidative stress, and antiapoptotic activity of targeted nitroxides.

Suppression of mitochondrial production of reactive oxygen species is a promising strategy against intrinsic apoptosis typical of degenerative diseases. Stable nitroxide radicals such as 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl (TEMPOL) and its analogs combine several important features, including recycleability, electron acceptance from respiratory complexes, superoxide dismutase mimicry, and radical scavenging. Although successful in antioxidant protection, their effective concentrations are too high for successful in vivo applications. Recently (J Am Chem Soc 127:12460, 2005), we reported that 4-amino 2,2,6,6-tetramethyl-1-piperidinyloxy, covalently conjugated to a five-residue segment of gramicidin S (GS), was integrated into mitochondria and blocked actinomycin D (ActD)-induced superoxide generation and apoptosis. Using a model of ActD-induced apoptosis in mouse embryonic cells, we screened a library of nitroxides to explore structure-activity relationships between their antioxidant/antiapoptotic properties and chemical composition and three-dimensional (3D) structure. High hydrophobicity and effective mitochondrial integration are necessary but not sufficient for high antiapoptotic/antioxidant activity of a nitroxide conjugate. By designing conformationally preorganized peptidyl nitroxide conjugates and characterizing their 3D structure experimentally (circular dichroism and NMR) and theoretically (molecular dynamics), we established that the presence of the beta-turn/beta-sheet secondary structure is essential for the desired activity. Monte Carlo simulations in model lipid membranes confirmed that the conservation of the d-Phe-Pro reverse turn in hemi-GS analogs ensures the specific positioning of the nitroxide moiety at the mitochondrial membrane interface and maximizes their protective effects. These new insights into the structure-activity relationships of nitroxide-peptide and -peptide isostere conjugates are instrumental for development of new mechanism-based therapeutically effective agents.

Animals↗

PubMed2006

Degradation of environmental endocrine disruptor di-2-ethylhexyl phthalate by a newly discovered bacterium, Microbacterium sp. strain CQ0110Y.

In this study di-2-ethylhexyl phthalate (DEHP)-degradation strain CQ0110Y was isolated from activated sludge. According to the biophysical/biochemical characteristics and analysis of 16S rDNA, the strain was identified as Microbacterium sp. The results of this study showed the optimal pH value and optimal temperature which influenced the degradation rate in wastewater: pH 6.5-7.5, 25-35 degrees C. Kinetics of degradation reaction had been performed at different initial concentrations and different time. Analyzed with SPSS10.0 software, the DEHP degradation can be described as the same exponential model when the initial DEHP concentration was lower than 1,350 mg/l. The kinetics equation was ln C = -0.4087t + A, with the degradation half life of DEHP in wastewater (1.59 days). To the best of our knowledge, this is the first reported case of DEHP degradation by Microbacterium sp. strain.

Actinomycetales↗

PubMed2006

Cerebellar 'transcriptome' reveals cell-type and stage-specific expression during postnatal development and tumorigenesis.

Disorders of cerebellar development can result in neurological disease and cancer. The identity of transcription factors that may uniquely mark and/or regulate development of single cerebellar cell types, however, is poorly understood. We used a library of approximately 1100 probes for expression of transcription factor (TF)-encoding genes (>70% of the mammalian 'transcriptome') to identify 227 genes with expression in developing neuronal and glial populations and 24 TFs that show cell-type- and stage-specific expression in granule cells, Purkinje cells and interneurons during postnatal cerebellar development. The utility of this panel is exemplified by analysis of medulloblastoma that shows upregulation of markers specific for early granule cell lineage, but not for other neuronal cell types, indicative of a unipotent precursor as well as a block in granule cell differentiation within the tumor. We propose that this atlas of the cerebellar transcriptome and the panel of 24 validated markers will be generally useful in analyses of mutations affecting postnatal cerebellar development and neoplasia.

Animals↗

PubMed2006

Investigation of a variety of cationic surfactants attached to cation-exchange silica for hydrophobicity optimization in admicellar solid-phase extraction for high-performance liquid and gas chromatography.

A series of cationic surfactants were attached to cation-exchange silica that included silica modified with sulfopropyl groups and unmodified silica to create hydrophobic solid-phase extraction sorbents. Various chain lengths and chain numbers of amine, ammonium and pyridinium-based cationic surfactants were investigated to reach sufficient sorbent hydrophobicity to capture US Environmental Protection Agency (EPA) priority polycyclic aromatic hydrocarbons (PAHs). Of the tested surfactant/silica combinations, dihexadecyldimethylammonium cations attached to unmodified silica resulted in the sorbent having the greatest hydrophobicity. This sorbent provided strong hydrophobic attraction of PAHs and also efficient elution because the PAHs were removed together with the surfactant using a very mild 5% acetic acid in methanol rinse solution. This admicellar solid-phase extraction procedure was applied for the determination of these PAHs for both high-performance liquid and gas chromatography. The detection limits of these PAHs were below the EPA's maximum contaminant level of 0.2 microg/L.

Cation Exchange Resins↗

PubMed2006

Replacement of the positively charged Walker A lysine residue with a hydrophobic leucine residue and conformational alterations caused by this mutation in MRP1 impair ATP binding and hydrolysis.

MRP1 (multidrug resistance protein 1) couples ATP binding/hydrolysis at its two non-equivalent NBDs (nucleotide-binding domains) with solute transport. Some of the NBD1 mutants, such as W653C, decreased affinity for ATP at the mutated site, but increased the rate of ATP-dependent solute transport. In contrast, other NBD1 mutants, such as K684L, had decreased ATP binding and rate of solute transport. We now report that mutations of the Walker A lysine residue, K684L and K1333L, significantly alter the tertiary structure of the protein. Due to elimination of the positively charged group and conformational alterations, the K684L mutation greatly decreases the affinity for ATP at the mutated NBD1 and affects ATP binding at the unmutated NBD2. Although K684L-mutated NBD1 can bind ATP at higher concentrations, the bound nucleotide at that site is not efficiently hydrolysed. All these alterations result in decreased ATP-dependent solute transport to approx. 40% of the wild-type. In contrast, the K1333L mutation affects ATP binding and hydrolysis at the mutated NBD2 only, leading to decreased ATP-dependent solute transport to approx. 11% of the wild-type. Consistent with their relative transport activities, the amount of vincristine accumulated in cells is in the order of K1333L> or =CFTR (cystic fibrosis transmembrane conductance regulator)>K684L>>>wild-type MRP1. Although these mutants retain partial solute transport activities, the cells expressing them are not multidrug-resistant owing to inefficient export of the anticancer drugs by these mutants. This indicates that even partial inhibition of transport activity of MRP1 can reverse the multidrug resistance caused by this drug transporter.

Adenosine Triphosphate↗

PubMed2006

Bioremediation of environmental endocrine disruptor di-n-butyl phthalate ester by Rhodococcus ruber.

In this study DBP-degradation strain CQ0301 was isolated from rubbish landfill soil. According to the biophysical, biochemical characteristics and analysis of 16S rRNA, the strain was identified as Rhodococcus ruber. Three new protein bands could be fractioned after DBP-inducing, which were suspected to participate the process of DBP-degrading. Catechol was suspected to be an intermediate product of DBP and cleaving the benzene ring was catalyzed by catechol 1,2-dioxygenase, because a highly activity of catechol 1,2-dioxygenase could be detected after DBP-inducing. The results of this study also showed the optimal pH value, optimal temperature which influenced the degradation rate in soil: pH 7.0-8.0, 30-35 degrees C. Kinetics of degradation reaction had been performed at different initial concentration and different time. Analyzed with SPSS10.0 software, the DBP degradation can be described as the same exponential model when the initial DBP concentration was lower than 50 mg/kg. The kinetics equation was lnC=-0.1332t + A, with the degradation half-life of DBP in soil (5.20 d). Inoculating CQ0301 could relieve DBP content in plant. We also found that adding nutrient materials into soil was useful for decreasing the DBP content in plant. In summary, we isolated a bacterium capable of degrading DBP and decreasing DBP content in plant. We also explored the mechanism of biodegradation and characterized the environmental factors influencing the degradation process in contaminated soil. Based on this work, we hope that these findings can provide some information for applying of bioremediation of DBP contaminated soil.

Biodegradation, Environmental↗

PubMed2006

[Association of baseline cholesterol level and its 10-year change with carotid atherosclerosis in the population of Peking University community].

OBJECTIVE: To explore the association of baseline cholesterol level in 1992 and its 10-year change from 1992 to 2002 with the prevalence of carotid atherosclerosis. METHODS: In 1992, 1985 subjects of the community of Peking University, aged 35 - 64, underwent physical examination and blood-lipid test to study the cardio-vascular disease (CVD) risk factors. In 2002, the second survey on CVD risk factors was conducted among the existing 1932 subjects, now aged 45 - 74. In addition, B-mode ultrasonography of the carotid artery was performed too. The complete data of 1331 subjects were analyzed. RESULTS: (1) In 2002, the prevalence rates of intimal medial thickening (IMT) and carotid plaque in the study population were 47.8% and 29.9% respectively. (2) The post-10-year prevalence rate of carotid plaque was 19.7% in the subjects with the baseline cholesterol < 3.64 mmol/L, and was 46.8% in those with the baseline cholesterol 6.24 mmol/L, with a thickening rate 3.1 times that of the subjects with the baseline cholesterol < 3.64 mmol/L. The higher the baseline TV level, the higher the prevalence rates of carotid plaque and IMT. (3) The prevalence rate of carotid plaque was 32.0% in the subjects with normal TC in both 1992 and 2002, and 50.0% in those with hypercholesterolemia in both 1992 and 2002. CONCLUSION: Carotid atherosclerosis is a prevalent disorder in the people aged 45 - 74 in Beijing. The prevalence rates of carotid plaque and IMT increase with the elevation of baseline cholesterol level.

Adult↗

PubMed2006

Influences on gene expression in vivo by a Shine-Dalgarno sequence.

The Shine-Dalgarno (SD+: 5'-AAGGAGG-3') sequence anchors the mRNA by base pairing to the 16S rRNA in the small ribosomal subunit during translation initiation. We have here compared how an SD+ sequence influences gene expression, if located upstream or downstream of an initiation codon. The positive effect of an upstream SD+ is confirmed. A downstream SD+ gives decreased gene expression. This effect is also valid for appropriately modified natural Escherichia coli genes. If an SD+ is placed between two potential initiation codons, initiation takes place predominantly at the second start site. The first start site is activated if the distance between this site and the downstream SD+ is enlarged and/or if the second start site is weakened. Upstream initiation is eliminated if a stable stem-loop structure is placed between this SD+ and the upstream start site. The results suggest that the two start sites compete for ribosomes that bind to an SD+ located between them. A minor positive contribution to upstream initiation resulting from 3' to 5' ribosomal diffusion along the mRNA is suggested. Analysis of the E. coli K12 genome suggests that the SD+ or SD-like sequences are systematically avoided in the early coding region suggesting an evolutionary significance.

Base Sequence↗

PubMed2006

Tumor necrosis factor receptor deficiency exacerbated Adriamycin-induced cardiomyocytes apoptosis: an insight into the Fas connection.

Cardiomyopathy is a major dose-limiting factor for applications of Adriamycin, a potent chemotherapeutic agent. The present study tested the hypothesis that increased tumor necrosis factor (TNF)-alpha signaling via its receptors protects against Adriamycin-induced cardiac injury. We used mice in which both TNF receptor I and II have been selectively inactivated (DKO) with wild-type mice as controls. Morphometric studies of cardiac tissue following Adriamycin treatment revealed greater ultrastructural damage in cardiomyocyte mitochondria from DKO mice. Biochemical studies of cardiac tissues showed cytochrome c release and the increase in proapoptotic protein levels, suggesting that lack of TNF-alpha receptor I and II exacerbates Adriamycin-induced cardiac injury. The protective role of TNF receptor I and II was directly confirmed in isolated primary cardiomyocytes. Interestingly, following Adriamycin treatment, the levels of Fas decreased in the wild-type mice. In contrast, DKO mice had an increase in Fas levels and its downstream target, mitochondrial truncated Bid. These results suggested that TNF-alpha receptors play a critical role in cardioprotection by suppression of the mitochondrial-mediated associated cell death pathway.

Animals↗

PubMed2006

Biological phosphorus removal with nitrite as election acceptor.

Biological phosphorus removal was studied in a sequencing batch reactor (SBR). The results showed that nitrite could be used as electron acceptor in denitrifying phosphorus removal. Feed mode of nitrite had significant influence on denitrifying phosphorus removal. Anoxic phosphorus assimilation rate could reach 10.44 mgP/gSS.h and the percentage of anoxic phosphorus assimilation amount was more than 97% with continuous feed mode. Granular sludge with denitrifying phosphorus removal activity was found in the SBR. The effects of different operational conditions, such as COD loading, settling time, HRT etc., on the formation of granules were also studied.

Biodegradation, Environmental↗

PubMed2006

[Effect of Bay K 8644 on arteriole smooth muscle cell membrane potential in rats with severe hemorrhagic shock].

OBJECTIVE: To investigate the effect of Ca(2+) influx through L-type Ca(2+) channels on normal and hyperpolarized membrane potential of arteriole smooth muscle cells (ASMCs) in rats. METHODS: The ASMCs isolated from normal rats and those with severe hemorrhagic shock were labeled with DiBAC4 (3) for membrane potential detection. RESULTS: Ca(2+) influx caused hyperpolarization of the membrane potential in the normal ASMCs but depolarization in the cells from rats with hemorrhagic shock, and this effect could be inhibited by TEA. CONCLUSION: Ca(2+)-activated potassium channels activated by Ca(2+) influx through L-type Ca(2+) channels in normal ASMCs to cause hyperpolarization but leads directly to membrane potential depolarization in ASMCs from rats with severe hemorrhagic shock. This finding can be meaningful for treatment of vascular hyporeactivity in advanced stage of severe shock.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2006

[Ultrastructural study of the pulmonary veins in pigs].

OBJECTIVE: To explore the possible relationship between the ultrastructural characteristics of pulmonary veins and the pathogenesis of atrial fibrillation originating from pulmonary veins. METHODS: The pulmonary veins from domestic pigs were serially sectioned (2 mm) transversely along the vessels. The odd number sections were fixed in 10% phosphate buffered formalin solution and the even number sections were fixed in 3% Glutaral for further electron microscopy observations. RESULTS: Two cell types were found in the pulmonary veins of pigs. One cell type was the P-like cells that had an empty-appearing cytoplasm containing only sparse myofibrils and small mitochondria, both of which were randomly distributed. Another cell type was slender transitional cells with plenty of longitudinally displayed myofibrils. CONCLUSION: P-like cells in the pig pulmonary veins were found using electron microscopy in this study and ectopic beats from P-like cells in the myocardial sleeves in the pulmonary veins might be responsible for atrial fibrillation originating from pulmonary veins.

Animals↗

PubMed2006

[Influences of orthodontic tooth movement on estrous cycle and estrogen in rats].

OBJECTIVE: To explore the influences of orthodontic tooth movement on estrous cycle and estrogen in female rats. METHODS: Two hundred female rats were divided into control group, one-time activation group, four-time activation group and sham-operated group. Each group was divided again into 4 sub-groups according to the different stage of the estrous cycle. The force-loading groups received repeated intermittent force. Serum estrogen was measured and the change of estrous cycle was recorded. RESULTS: There were significant variations in the estrogen level among the groups which received mechanical force during the same stage of the estrous cycle (P < 0.01) and among the subgroups within each group (P < 0.05). These experimental treatments affected the estrous cycle of the rats in the groups received force in metestrus and diestrus. CONCLUSIONS: Estrus of rats was the appropriate time for the orthodontic force.

Animals↗

PubMed2006

[Integrin 3 mRNA changes after orthodontic teeth movement in periodontitis rats].

OBJECTIVE: To study the integrin beta3 mRNA changes after orthodontic treatment on normal teeth and periodontitis teeth in rats. METHODS: 96 adult SD rats of 10 weeks old were randomly divided into normal tooth move-ment group and periodontitis tooth movement group. The rats in the two groups were sacrificed after 0 d, 12 h, 1 d, 3 d, 5 d and 7 d of tooth movement. The alveolar specimens were prepared. The integrin beta3 mRNA were detected using in situ hybridization in the specimens. The OD index of positively stained osteoclasts for integrin beta3 mRNA after orthodontic tooth movement in the two groups were measured and compared. RESULTS: There were weak positive signals on the cytoplasm of osteoclasts in periodontum in both groups after 12 hours and 3 days force activation. No positive signals were detected in the rest samples. There was no difference in the OD of positive stained osteoclasts between normal and periodontitis groups. Strong expressions were present on cells with one or two nuclei in the alveolar marrow. CONCLUSION: It is suggested that integrin beta3 mRNA is related with osteoclasts maturation and migration in orthodontic tooth movement.

Animals↗

PubMed2006

[Dimensional differences in craniofacial morphologies of prepubescence Class II patients with deep and shallow mandibular antegonial notching].

OBJECTIVE: To identify certain craniofacial characteristics of untreated prepubescence Class II patients with deep and shallow mandibular notching. METHODS: 18 untreated preadolescent Class II patients with deep mandibular notching and 17 untreated preadolescent Class II patients with shallow mandibular notching were selected. Each subject's pretreatment lateral cephalogram was traced. Seventeen angular and eleven linear measurements were made. The means and standard deviations were calculated for each parameter. The significance of difference between mean values was evaluated by the Independent-Samples T test. Differences were considered statistically significant when the P value was 0.05 or less. RESULTS: There was no difference in ANB between two groups, but deep notch cases had more retrusive maxillary and mandibles with shorter maxillary and corpus. In vertical direction, subjects with a deep mandibular notch had a longer lower facial height and more vertically directed mandibular plane angle than did shallow notch cases, these may be caused by the increasing of alveolar height of maxillary, smaller ramus height and greater gonial angle. CONCLUSION: There were some differences in the craniofacial morphologies between deep and shallow notching groups of preadolescent Class II patients. Compared with shallow notching group, the mandibles with the deep notching rotated downward and backward and have more vertical directed tendency, but there have no obviously difference in horizontal relationship of maxillary and mandible between two groups.

Cephalometry↗