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Biomedical subjects

Yan Zhao

Publications and source records attributed to Yan Zhao.

At least 55 records · Page 3Linked to original sources

Spectroscopy property of Ag nanoparticles.

Three silver nanoparticles of different size characterized by the UV-vis absorbance spectra and TEM images were prepared by citrate reduction and laser ablation with excitation of 532 and 248 nm. It is proved that all of them are effective SERS-active substrates, whereas, enhancement effect of silver colloids has not too much relation with the size and shape of the Ag nanoparticles. However, different photoluminescence spectra were observed from these three particles, indicating that the photoluminescence property of silver nanoparticles is dependent on the size. The spectra shift to higher energies with decreasing particle size. In addition, we also tentatively give the assignment of the luminescence bands.

Metal Nanoparticles↗

Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441.

DNA double-strand breaks (DSB) are the most cytotoxic lesions induced by ionizing radiation and topoisomerase II poisons, such as etoposide and doxorubicin. A major pathway for the repair of DSB is nonhomologous end joining, which requires DNA-dependent protein kinase (DNA-PK) activity. We investigated the therapeutic use of a potent, specific DNA-PK inhibitor (NU7441) in models of human cancer. We measured chemosensitization by NU7441 of topoisomerase II poisons and radiosensitization in cells deficient and proficient in DNA-PK(CS) (V3 and V3-YAC) and p53 wild type (LoVo) and p53 mutant (SW620) human colon cancer cell lines by clonogenic survival assay. Effects of NU7441 on DSB repair and cell cycle arrest were measured by gammaH2AX foci and flow cytometry. Tissue distribution of NU7441 and potentiation of etoposide activity were determined in mice bearing SW620 tumors. NU7441 increased the cytotoxicity of ionizing radiation and etoposide in SW620, LoVo, and V3-YAC cells but not in V3 cells, confirming that potentiation was due to DNA-PK inhibition. NU7441 substantially retarded the repair of ionizing radiation-induced and etoposide-induced DSB. NU7441 appreciably increased G(2)-M accumulation induced by ionizing radiation, etoposide, and doxorubicin in both SW620 and LoVo cells. In mice bearing SW620 xenografts, NU7441 concentrations in the tumor necessary for chemopotentiation in vitro were maintained for at least 4 hours at nontoxic doses. NU7441 increased etoposide-induced tumor growth delay 2-fold without exacerbating etoposide toxicity to unacceptable levels. In conclusion, NU7441 shows sufficient proof of principle through in vitro and in vivo chemosensitization and radiosensitization to justify further development of DNA-PK inhibitors for clinical use.

Animals↗

Ethological analysis of scopolamine treatment or pretreatment in morphine dependent rats.

Although scopolamine is currently used to treat morphine addiction in humans, its extensive actions on behaviors have not been systematically analyzed yet, and the underlying mechanisms of its effects still remain ambiguous. The present study was carried out to clarify the possible mechanisms by evaluating the effects of scopolamine pretreatment and treatment on naloxone-precipitated withdrawal signs and some of other general behaviors in morphine dependent rats. Our results showed that scopolamine pretreatment and treatment attenuated naloxone-precipitated withdrawal signs including jumping, writhing posture, weight loss, genital grooming, teeth-chattering, ptosis, diarrhea and irritability, except for wet dog shakes, while general behaviors such as water intake, urine volume and morphine excretion in urine were increased. Our findings suggest that scopolamine has significant actions in the treatment of opiate addiction, which might result from increasing morphine excretion from urine.

Analysis of Variance↗

Identification of a basic helix-loop-helix transcription factor expressed in mammary gland alveolar cells and required for maintenance of the differentiated state.

The development of mammary glands relies on complicated signaling pathways that control cell proliferation, differentiation, and apoptotic events through transcriptional regulatory circuits. A key family of transcription factors used in mammary gland development is the helix-loop-helix/basic helix-loop-helix (HLH/bHLH) protein family. In this study, we identify Mist1 as a tissue-restricted Class II bHLH transcription factor expressed in lactating mammary glands. Mouse and human mammary glands accumulated Mist1 protein exclusively in secretory alveolar cells, and Mist1 transcripts were differentially expressed in mouse SCp2 cells induced to differentiate by addition of lactogenic hormones. Mist1 null (Mist1(KO)) lactating mammary glands were defective in normal lobuloalveolar organization, exhibiting shedding of cells into the alveolus lumen and premature activation of the signal transducer and activator of transcription 3 signaling pathway. These cells also failed to maintain expression of the gap junction proteins connexin26 and connexin32, leading to the loss of gap junctions. Our findings suggest that loss of Mist1 impairs the maintenance of the fully differentiated alveolar state and, for the first time, places Mist1 within the hierarchy of known HLH/bHLH proteins that control mammary epithelial cell development.

Animals↗

Comparative DFT study of van der Waals complexes: rare-gas dimers, alkaline-earth dimers, zinc dimer, and zinc-rare-gas dimers.

Recent interest in the application of density functional theory prompted us to test various functionals for the van der Waals interactions in the rare-gas dimers, the alkaline-earth metal dimers, zinc dimer, and zinc-rare-gas dimers. In the present study, we report such tests for 18 DFT functionals, including both some very recent functionals and some well-established older ones. We draw the following conclusions based on the mean errors in binding energies and complex geometries: (1) B97-1 gives the best performance for predicting the geometry of rare-gas dimers, whereas M05-2X and B97-1 give the best energetics for rare-gas dimers. (2) PWB6K gives the best performance for the prediction of the geometry of the alkaline-earth metal dimers, zinc dimers, and zinc-rare-gas dimers. M05-2X gives the best energetics for the metal dimers, whereas B97-1 gives the best energetics for the zinc-rare-gas dimers. (3) The M05 functional is unique in providing good accuracy for both covalent transition-metal dimers and van der Waals metal dimers. (4) The combined mean percentage unsigned error in geometries and energetics shows that M05-2X and MPWB1K are the overall best methods for the prediction of van der Waals interactions in metal and rare-gas van der Waals dimers.

Computer Simulation↗

[Clinical analysis of pneumomediastinum complicated in polymyositis and dermatomyositis].

OBJECTIVE: To analyze the clinical features of pneumomediastinum complicated in polymyositis and dermatomyositis (PM/DM) and to study the pathogenesis thereof. METHODS: The clinical data of 4 patients with pneumomediastinum complicated in dermatomyositis out of 447 PM/DM patients hospitalized in Peking Union Medical College (PUMC) Hospital Jan 1989 to June 2005, were analyzed. The records of patients with PM/DM available in English throughout the world were reviewed to collect those with pneumomediastinum as a complication. And the data of these patients were analyzed, focusing mainly on the age, gender, peak of serum creatine kinase (CK), presence of pneumomediastinum, cutaneous vasculopathy, chest radiographic changes, tracheal cannula, management, and outcome. RESULTS: Among the 447 patients with PM/DM hospitalized in PUMC Hospital, 134 males and 313 females, aged 42 +/- 17, pneumomediastinum was observed as a complication in four patients, 3 males and 1 female, aged 12 - 43, with a prevalence rate of 0.9%. Together with 17 cases reported in the English literatures there were 21 patients with pneumomediastinum complicated in polymyositis and dermatomyositis (PM/DM in all. Only one of the literatures reported a prevalence rate as high as 8.3% (4/48), and other literatures were merely case reports. Compared with the PM/DM patients without pneumomediastinum the mean age of the PM/DM patients with pneumomediastinum was significantly younger (34:42, P < 0.01), the male: female ratio significantly higher (13:8 to 132:311, P < 0.01), the morbidity rates of interstitial lung disease and of cutaneous vasculopathy significantly higher (18/21 to 134/443, and 12/21 to 44/443, both P < 0.01). Although statistic analysis could not be undertaken because of the peak of CK not being provided in details in the literatures, the CK levels of the patients with pneumomediastinum were mostly normal or mildly higher with a peak lower than 500 U/L Three of the 4 patients with pneumomediastinum hospitalized in PUMC Hospital and 5 of the 443 patients (1.1%) without this complication received tracheal cannula. There was a significant association of pneumomediastinum with tracheal cannula (P = 0.000). CONCLUSION: Vasculopathy is strongly suspected as being responsible for the pneumomediastinum in DM, and male gender, younger age, interstitial lung disease, and tracheal cannula may be the risk factors of this pneumomediastinum complicated in PM/DM.

Adolescent↗

Fluoride levels in various black tea commodities: measurement and safety evaluation.

In order to determine the fluoride content of various products of black tea and to make safety evaluations, 37 commodities in the different manufactured forms of tea were assessed by means of ion-selective electrode and spectrophotometric methods. The results showed wide differences in fluoride levels. The fluoride content was found 0.95-1.41 mg/L in black tea sticks, 0.70-2.44 mg/L in black tea granules and 1.15-6.01 mg/L in black tea bags. Of the products tested, the fluoride content was greatest in black tea bags, presumably because black tea bags are made of low cost, and older tea leaves. According to WHO's recommendation, fluoride exposure threshold for children is 2mg of daily intake and for adult, 4 mg. Assuming that children's daily intake of black tea was 800 ml and adult's 1500 ml, 56% of black tea bags should be considered unsafe for children and 44% should be considered unsafe for adults. At average rates of consumption, 24% of the black tea bags could result in an increasing risk of osteofluorosis and fractures (WHO). In the areas with drinking water fluoridation or other fluoride supplements, excessive fluoride exposure can become even more severe with even lower intake tea made from black tea bags. The potential hazards of fluoride arising from consumption of black tea has not aroused due public attention. Therefore, it is necessary to establish reliable fluoride surveillance in food and beverage commodities and conduct additional epidemiological research on fluoride hazards. In addition, it is urgent that governmental and international agencies adopt safe standards of fluoride content in tea commodities.

Electrochemistry↗

[Clinical research of primary intraspinal hemangiopericytoma].

OBJECTIVE: To investigate the effective means of treatment for primary intraspinal hemangiopericytoma. METHODS: The clinical presentation, imaging features, treatment and prognosis of 23 cases of intraspinal hemangiopericytoma, 14 males and 9 females, aged 39.1 (14 - 65), were analyzed retrospectively. RESULTS: Subtotal resection was performed on 11 cases, subtotal resection and radiotherapy on 4 cases, total resection on 5 cases, and total resection and radiotherapy on 3 cases. Spinal stabilization was conducted on 2 cases after total resection with severe damage of the vertebral body or pedicle of vertebral arch. Nineteen cases were followed up for 3.8 years (6 months-10 years). The recurrence rate was 68% and the metastasis rate was 21%. CONCLUSION: Primary intraspinal hemangiopericytoma should be resected en bloc with neighboring dura mater to reduce blood loss and recurrence. Resection of large lesions may be safer after preoperative embolization. The patients undergoing subtotal resection need adjuvant radiotherapy. The patients with evident spinal involvement may benefit from spinal stabilization. Lesions arising from dural mater have better prognosis. Postoperative long-term follow-up is necessary.

Adolescent↗

Enantiomeric separation of synthetic 2,3-dihydroxy-3-phenylpropionate compounds by beta-cyclodextrin-modified capillary electrophoresis.

A new capillary electrophoretic method was developed for enantiomeric separation and optical impurity analysis of three synthetic 2,3-dihydroxy-3-phenylpropionate compounds using native beta-cyclodextrin (beta-CD) as chiral selector and borate as a background electrolyte. The separation was carried out in uncoated capillary (58.5 cm x 75 microm I.D., effective length 48.5 cm). The results showed that beta-CD as the chiral selector exhibited good enantioselectivity and the baseline separation was obtained at pH 9.8, 200 mM borate buffer containing 1.7% beta-CD at applied voltage 15 kV and capillary temperature 20 degrees C within 15 min. The precision of each tested compound was less than 1.0% at migration time and 5.0% in corrected peak area and the accuracy of the method was in the range of 98.7-105%. Furthermore, the developed method was successfully applied to the determination of the undesirable trace (2S,3R)-(+)-form impurity in the synthetic (2R,3S)-(-)-2,3-dihydroxy-3-phenylpropionate samples.

Buffers↗

Characterization and functional analysis of a pollen-specific gene st901 in Solanum tuberosum.

A pollen-specific gene, sb401, which was isolated from a cDNA library of in vitro geminated pollen of the diploid potato species Solanum berthaultii, belongs to the class of genes expressed late during pollen development. Using sb401 as a probe, a pollen-specific gene st901 was isolated from the genomic library of a potato species Solanum tuberosum cv. Desiree. Sequencing and RT-PCR analysis showed that the st901 genomic gene is 2,889 bp long, contains three exons and two introns, and encodes a putative polypeptide of 217 residues. The predicted protein sequence contains four imperfect repeated motifs of V-V-E-K-K-N/E-E; the core sequence of the repeats (K-K-N/E-E) resembles a microtubule-binding domain of the microtubule-associated protein MAP1B from mouse. The examination of a promoter-reporter construct in transgenic potato plants revealed that the st901 is expressed exclusively in mature pollen grains, which is consistent with the results of Northern blot and RT-PCR. For analysis of the function of st901, transgenic plants harboring antisense copies of st901 cDNA driven by a native st901 promoter were generated. Suppression of st901 gene in potato resulted in aberrant pollen at maturation and pollen viability of transgenic plants ranged from 4.4 to 14.8%, while that of control plants were more than 90%. These results strongly suggest that st901 has an essential role in pollen development.

Amino Acid Sequence↗

Combined valence bond-molecular mechanics potential-energy surface and direct dynamics study of rate constants and kinetic isotope effects for the H + C2H6 reaction.

This article presents a multifaceted study of the reaction H+C(2)H(6)-->H(2)+C(2)H(5) and three of its deuterium-substituted isotopologs. First we present high-level electronic structure calculations by the W1, G3SX, MCG3-MPWB, CBS-APNO, and MC-QCISD/3 methods that lead to a best estimate of the barrier height of 11.8+/-0.5 kcal/mol. Then we obtain a specific reaction parameter for the MPW density functional in order that it reproduces the best estimate of the barrier height; this yields the MPW54 functional. The MPW54 functional, as well as the MPW60 functional that was previously parametrized for the H+CH(4) reaction, is used with canonical variational theory with small-curvature tunneling to calculate the rate constants for all four ethane reactions from 200 to 2000 K. The final MPW54 calculations are based on curvilinear-coordinate generalized-normal-mode analysis along the reaction path, and they include scaled frequencies and an anharmonic C-C bond torsion. They agree with experiment within 31% for 467-826 K except for a 38% deviation at 748 K; the results for the isotopologs are predictions since these rate constants have never been measured. The kinetic isotope effects (KIEs) are analyzed to reveal the contributions from subsets of vibrational partition functions and from tunneling, which conspire to yield a nonmonotonic temperature dependence for one of the KIEs. The stationary points and reaction-path potential of the MPW54 potential-energy surface are then used to parametrize a new kind of analytical potential-energy surface that combines a semiempirical valence bond formalism for the reactive part of the molecule with a standard molecular mechanics force field for the rest; this may be considered to be either an extension of molecular mechanics to treat a reactive potential-energy surface or a new kind of combined quantum-mechanical/molecular mechanical (QM/MM) method in which the QM part is semiempirical valence bond theory; that is, the new potential-energy surface is a combined valence bond molecular mechanics (CVBMM) surface. Rate constants calculated with the CVBMM surface agree with the MPW54 rate constants within 12% for 534-2000 K and within 23% for 200-491 K. The full CVBMM potential-energy surface is now available for use in variety of dynamics calculations, and it provides a prototype for developing CVBMM potential-energy surfaces for other reactions.

Journal Article↗

Fluorescence study of fullerene in organic solvents at room temperature.

At room temperature, fluorescence spectra for C60 in organic solvents of four typical kinds have been reported, which indicate that intensity of fluorescence and fine structure of fluorescence peaks are dependent on the interaction between C60 and solvent. It is shown that the solvents of effective electron donors could make a comparatively strong interaction with fullerenes due to formation of the charge transfer adduct, which could greatly distort the molecular symmetry, leading to the strong and well-resolved fluorescence. The strong fluorescence spectra for C70 in room temperature solutions are also observed.

Fluorescence↗

Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation: identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer.

Androgen and androgen receptor (AR)-mediated signaling are crucial for the development of prostate cancer. Identification of novel and naturally occurring phytochemicals that target androgen and AR signaling from Oriental medicinal herbs holds exciting promises for the chemoprevention of this disease. In this article, we report the discovery of strong and long-lasting antiandrogen and AR activities of the ethanol extract of a herbal formula (termed KMKKT) containing Korean Angelica gigas Nakai (AGN) root and nine other Oriental herbs in the androgen-dependent LNCaP human prostate cancer cell model. The functional biomarkers evaluated included a suppression of the expression of prostate-specific antigen (PSA) mRNA and protein (IC50, approximately 7 microg/mL, 48-hour exposure) and an inhibition of androgen-induced cell proliferation through G1 arrest and of the ability of androgen to suppress neuroendocrine differentiation at exposure concentrations that did not cause apoptosis. Through activity-guided fractionation, we identified decursin from AGN as a novel antiandrogen and AR compound with an IC50 of approximately 0.4 microg/mL (1.3 micromol/L, 48-hour exposure) for suppressing PSA expression. Decursin also recapitulated the neuroendocrine differentiation induction and G1 arrest actions of the AGN and KMKKT extracts. Mechanistically, decursin in its neat form or as a component of AGN or KMKKT extracts inhibited androgen-stimulated AR translocation to the nucleus and down-regulated AR protein abundance without affecting the AR mRNA level. The novel antiandrogen and AR activities of decursin and decursin-containing herbal extracts have significant implications for the chemoprevention and treatment of prostate cancer and other androgen-dependent diseases.

Androgen Antagonists↗

Analysis of optical purity and impurity of synthetic D-phenylalanine products using sulfated beta-cyclodextrin as chiral selector by reversed-polarity capillary electrophoresis.

A new capillary electrophoresis (CE) method has been achieved for simultaneous separation and quantification of phenylalanine, N-acetylphenylalanine enantiomers, and prochiral N-acetylaminocinnamic acid, possibly co-existent in reaction systems or synthesized products of D-phenylalanine. The separation was carried out in an uncoated capillary under reversed-electrophoretic mode. Among the diverse charged cyclodextrins (CDs) examined, highly sulfated (HS)-beta-CD as the chiral selector exhibited the best enantioselectivity. The complete separation of the analytes was obtained under the optimum conditions of pH 2.5, 35 mM Tris buffer containing 4% HS-beta-CD, applied voltage -15 kV, and capillary temperature 25 degrees C. Furthermore, the proposed method was applied to the determination of optical purity and trace impurities in three batches of the asymmetric synthetic samples of D-phenylalanine, and satisfactory results were obtained. The determination recoveries of the samples were in the range of 97.8-103.8%, and precisions fell within 2.3-5.0% (RSD). The results demonstrate that this CE method is a useful, simple technique and is applicable to purity assays of D-phenylalanine.

Catalysis↗

Vitamin E analogues as anticancer agents: lessons from studies with alpha-tocopheryl succinate.

The new millennium has witnessed considerable decrease in a number of previously fatal pathologies, largely due to the advancement in molecular medicine and modern approaches to treatment. In spite of this success, neoplastic disease remains a serious problem due to several reasons. These include an exceedingly high variability of cancer cells even within the same type of tumour. Cancer cells, albeit of clonal origin, mutate so that they escape established treatments, resulting in the fatal outcome of current therapies. Moreover, there are types of cancer, such as mesotheliomas, that cannot be treated at present. A novel group of clinically interesting anticancer drugs has been a recent focus in the literature that hold substantial promise as selective anticancer drugs. These compounds, epitomised by alpha-tocopheryl succinate, comprise redox-silent analogues of vitamin E that have been shown to suppress several types of cancer in animal models, including breast, colon and lung cancer as well as mesotheliomas and melanomas, while being nontoxic to normal cells and tissues. It is now proven that the strong anticancer effect of vitamin E analogues stems from their propensity to induce selective apoptosis in malignant cells. The results point to the novel group of vitamin E analogues as promising agents applicable to different types of tumours.

Animals↗

Changes of nuclear matrix proteins following the differentiation of human osteosarcoma MG-63 cells.

Human osteosarcoma MG-63 cells were induced into differentiation by 5 mmol/L hexamethylene bisacetamide (HMBA). Their nuclear matrix proteins (NMPs) were selectively extracted and subjected to two-dimensional gel electrophoresis analysis. The results of protein patterns were analyzed by Melanie software. The spots of differentially expressed NMPs were excised and subjected to in situ digestion with trypsin. The maps of peptide mass fingerprinting were obtained by MALDI-TOF-MS analysis, and were submitted for NCBI database searches by Mascot tool. There were twelve spots changed remarkably during the differentiation induced by HMBA, nine of which were identified. The roles of the regulated proteins during the MG-63 differentiation were analyzed. This study suggests that the induced differentiation of cancer cells is accompanied by the changes of NMPs, and confirms the presence of some specific NMPs related to the cancer cell proliferation and differentiation. The changed NMPs are potential markers for cancer diagnosis or targets for cancer therapy.

Cell Differentiation↗

Formation of acrolein adducts with 2'-deoxyadenosine in calf thymus DNA.

Acrolein is a ubiquitous environmental contaminant that has been found to be mutagenic in prokaryotic and eukaryotic cells. In the present study, we examined the reactions of acrolein with 2'-deoxyadenosine and calf thymus single- and double-stranded DNA in aqueous buffered solutions at physiological conditions. The deoxynucleoside adducts were isolated by reversed-phase liquid chromatography, and their structures were determined by their UV absorbance, mass spectrometry, and 1H and 13C NMR spectroscopy. The reaction of 2'-deoxyadenosine with acrolein resulted in the formation of four structurally different adducts (dAI, dAII, dAIII, dAIV). The structures of the novel acrolein adducts, dAIII and dAIV, were assigned as 3-[N(6)-(2'-deoxyadenosinyl)]propanal (dAIII) and 9-(2'-deoxyribosyl-6-(3-formyl-1,2,5,6-tetrahydropyridyl)purine (dAIV), respectively. The adduct dAIII was found to arise via a Dimroth rearrangement of adduct dAI, while the adduct dAIV was shown to be formed upon further reaction of acrolein with dAIII. In the reaction of acrolein with calf thymus DNA, all studied 2'-deoxyadenosine-acrolein adducts were observed. For the first time, it is shown that the N(6)-adduct and the adducts which are derived from two acrolein units are formed in calf thymus DNA.

Acrolein↗

Electrophysiological evidence for the interaction of substance P and glutamate on Adelta and C afferent fibre activity in rat hairy skin.

1. The purpose of the present study was to investigate whether there was a cooperative interaction between substance P (SP) and glutamate (GLU) administered subcutaneously on Adelta and C primary afferent fibre activity in dorsal hairy skin of the rat in vivo. The single unit activities of Adelta and C afferent fibres were recorded by isolation of fibre filaments from the dorsal cutaneous nerve branches and the effects of subcutaneous injections of low doses of SP, GLU and SP + GLU on activity were determined. 2. Sub-threshold doses of SP (1 micro mol/L, 10 microL) administered subcutaneously into the dorsal hairy skin had no effect on the afferent discharges of either Adelta or C units. 3. The afferent discharges of 35% (11/31) of Adelta fibres and 33% (6/18) of C fibres were increased by local injection of the submaximal doses of GLU (10 micro mol/L, 10 microL) into the receptive fields. 4. The GLU-induced excitatory response was significantly enhanced by coinjection of subthreshold doses of SP. The mean discharge rates of Adelta fibres and C fibres were increased from 5.84 +/- 1.54 and 5.02 +/- 2.65 impulses/min to 19.91 +/- 4.35 and 17.58 +/- 5.59 impulses/min, respectively, whereas the excitatory proportions of Adelta and C fibres were increased from 35 and 33% to 84 and 83%, respectively. The duration of the excitation for Adelta fibres and C fibres was also significantly increased after coinjection of SP + GLU compared with that observed when either substance was given alone. 5. The present study provides electrophysiological evidence for an interaction between receptors for SP and GLU on the fine fibres activities in rat hairy skin, which may be involved in the mechanisms of hyperalgesia.

Animals↗