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Biomedical subjects

Yanling Zhang

Publications and source records attributed to Yanling Zhang.

At least 37 records · Page 2Linked to original sources

The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation.

Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1alpha cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1alpha in pancreatic beta cells. Expression of collectrin was decreased in the islets of HNF-1alpha (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the beta cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca(2+) influx. Conversely, suppression of collectrin attenuated insulin secretion. Collectrin bound to SNARE complexes by interacting with snapin, a SNAP-25 binding protein, and facilitated SNARE complex formation. Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis.

Animals↗

Cytotoxic cembranoid diterpenes from a soft coral Sinularia gibberosa.

Five new alpha-methylene-gamma-lactone-bearing cembranoid diterpenes, sinularolides A-E (1-5), along with 10 known cembranoids, were isolated from the soft coral Sinularia gibberosa. Their structures were determined by extensive spectroscopic (IR, MS, 2D NMR) data analysis. Compounds 2-5 showed moderate activity against selected tumor cell lines.

Animals↗

Development of HPLC methods for the determination of cyadox and its main metabolites in goat tissues.

Rapid and sensitive high-performance liquid-chromatographic methods were developed for the determination of cyadox, an antimicrobial growth-promoter, and its main metabolites (1,4-bisdesoxycyadox, quinoxaline-2-carboxylic acid) in goat muscle, liver, kidney and fat. Cyadox (CYX) and 1,4-bisdesoxycyadox (BDCYX) in fat were extracted with acetonitrile, and in other tissues with ethyl acetate. Quinoxaline-2-carboxylic acid (QCA) was isolated from tissue hydrolysates by solvent extraction, cleaned up with ion-exchange chromatography, followed by a final liquid-liquid extraction step. UV detections of CYX, BDCYX and QCA were performed at 305, 280 and 320 nm, respectively. The average recoveries of CYX, BDCYX and QCA in spiked tissues at levels of 25, 50, 100 microg/kg were 65 - 92%. The inter-day relative standard deviation for three compounds in different tissues was 5 - 16%. The quantitation limit was 25 microg/kg, and the detection limit was 15 microg/kg for three compounds in various tissues. Incurred goat tissues were analyzed to demonstrate the validity of the described methodologies. The present methods were highly selective and could be used in the metabolism and residue studies of cyadox.

Animals↗

Gene delivery of Tim44 reduces mitochondrial superoxide production and ameliorates neointimal proliferation of injured carotid artery in diabetic rats.

Hyperglycemia induces the production of reactive oxygen species (ROS) from mitochondria, which is closely related to diabetic vascular complications. Mammalian translocase of inner mitochondrial membrane (Tim)44 was identified by upregulation in streptozotocin (STZ)-induced diabetic mouse kidneys; Tim44 functions as a membrane anchor of mtHsp70 to TIM23 complex and is involved in the import of preproteins with mitochondria-targeted presequence into mitochondrial matrix. The process is dependent on inner membrane potential (Delta psi) and ATP hydrolysis on ATPase domain of mtHsp70. Here, we show that the gene delivery of Tim44 using pcDNA3.1 vector (pcDNA3.1/TIM44) into the balloon injury model of STZ-induced diabetic rats ameliorated neointimal proliferation. ROS production, inflammatory responses, and cell proliferation in injured carotid artery were diminished by delivery of pcDNA3.1/TIM44. In vitro experiments using human aortic smooth muscle cells (HASMCs) revealed that the gene delivery of Tim44 normalized high-glucose-induced enhanced ROS production and increased ATP production, alterations in inner membrane potential, and cell proliferation. Transfection of siRNA and pcDNA3.1/TIM44 using HASMC culture clarified that import of antioxidative enzymes such as superoxide dismutase and glutathione peroxidase was facilitated by Tim44. Tim44 and its related molecules in mitochondrial import machinery complex are novel targets in the therapeutic interventions for diabetes and its vascular complications.

Adenosine Triphosphate↗

[Study on relationship between three-dimensional quantitative structure and retention parameters of chromatography].

A novel method to predict retention parameters of liquid chromatography is developed. By determining their lowest energy conformation, molecules are aligned according to one specific rule and the scope of the molecular field is defined around the aligned molecules. A positively charged sp3 carbon probe atom is used to calculate the characters of the molecular field such as the electrostatic and steric interaction energies. Then partial least square (PLS) method is exploited to analyze relationships between the a, c parameters of compounds and characters of the molecular field and finally comparative molecular field analysis (CoMFA) models are built, which are exploited to study three-dimensional quantitative structure-retention relationship (QSRR) between the a, c parameters of compounds in methanol/water on a reversed-phase C18 column and the characters of the molecular field. The models are applied to four different forms of arenes: alkylation-substituted benzenes, multi-ring arenes, chlorobenzenes and dinitro-substituted arenes. The results of PLS analyses show that three-dimensional models are obtained from the first three forms. The cross-validated q2 of the first three models are all above 0.5 and the non-cross-validated r2 of the first two forms are even above 0.995, so the predictive abilities of these models are considerable. The model of dinitro-substituted arenes is not so reasonable. The possible reason is that the nitro-substitutions are on different benzene rings. The novel method explored can be utilized to predict the retention parameters of the compounds, which are unknown but have the same kind of structure with the known compounds, and also provide information about the class of the compounds. The results of this project can be applied to direct the further study of the relationship between three-dimensional quantitative structure and retention parameters of liquid chromatography.

Benzene Derivatives↗

[Exploratory study of factors related sexual dysfunction among cancer patients].

OBJECTIVE: To investigate the factors related to the sexual dysfunction among cancer patients and make preparation for its prevention and treatment to improve the quality of life of cancer patients. METHODS: Self-designed questionnaires about sexual function were used and 130 patients in their rehabilitation period interviewed. These patients were suffering from different kinds of cancer. RESULTS: Age of patients and their perception of sex are two important factors resulting in significant difference of suffering rate of sexual dysfunction among these cancer patients. The total suffering rate of sexual dysfunction among patients suffering from reproductive cancer is significantly higher than that of patients suffering from cancer in other systems. Of all the factors we analyzed in the research, we found that stage of cancer; physical strength and perception of sex had significant correlation with newly emerging sexual dysfunction. From the patient's point of view, those newly suffering from sexual dysfunction after their cases were diagnosed as cancer thought that cancer treatment had negative effect on their sexual function. CONCLUSION: Stage of cancer, physical strength and perception of sex had significant correlation with sexual dysfunction of cancer patients who have received cancer treatment. This suggests that, intervention in patients' wrong perception of sex is the first aspect we should pay attention to in treating and preventing sexual dysfunction among cancer patients.

Adult↗

Synthesis and infrared and fluorescence spectral properties of luminescent terbium and europium complexes with open-chain carboxylate crown ethers.

Two open-chain carboxylate crown ether ligands and their terbium(III) and europium(III) complexes were synthesized and characterized. The terbium and europium ions were found to coordinate to the carboxylate oxygens. The fluorescence properties of europium complexes in the solid state and terbium complexes in the solid state and in the organic solvent were studied in detail, respectively. Under the excitation of ultraviolet light, strong green fluorescence of solid terbium complexes and red fluorescence of solid europium complexes were observed. These observations show that the two ligands favor energy transfer to the emitting energy level of Tb(3+). Some factors that influencing the fluorescent intensity were also discussed.

Carboxylic Acids↗

[Grain contents of Cd, Cu and Se by 57 rice cultivars and the risk significance for human dietary uptake].

Field experiment on uptake and accumulation of Cd, Cu and Se in grains by 57 rice cultivars grown on a single Wuzhatu (a black heavy soil) in Jiangsu Province were conducted. The grain concentrations of Cd, Cu and Se varied in the range of 0.099 +/- 0.039, 4.86 +/- 2.595, 0.035 +/- 0.007 mg/kg respectively, demonstrating remarkable inter-species difference in heavy metal accumulation in rice grains. Cd uptake and accumulation in grains followed that of Cu by the studied cultivars. However, high Se uptake and accumulation tended to suppress Cu and Cd uptake and accumulation in grains. By calculation using the RfD values recommended by USEPA and WHO respectively, human health risk was shown to be possible from consuming the rice grains from these varieties by a Chinese diet. The Cd concentration of 92% of the varieties was found over the permissible limit recommended by USEPA. Thus, attention must be paid to extensive cultivation of high Cd accumulation cultivars of rice in polluted rice soils. For grain accumulation of Se was usually associated with low Cu and Cd accumulation, rice breeding with improvement of rice Se level would be possible for production of high quality of rice.

Cadmium↗

p14ARF upregulation of p53 and enhanced effects of 5-fluorouracil in pancreatic cancer.

OBJECTIVE: To investigate the synergistic antitumor effects of combined use of p14ARF gene and 5-fluorouracil (5-Fu) in pancreatic cancer. METHODS: A human pancreatic cancer cell line PC-3 was transfected with lipofectin-mediated recombinant p14ARF gene, and was then administered with 5-Fu. Cell growth, morphological changes, cell cycle, apoptosis, and molecular changes were measured using the MTT assay, flow cytometry, RT-PCR, Western blotting, and immunocytochemical assays. RESULTS: After transfection of p14ARF, cell growth was obviously inhibited, resulting in an accumulation of cells in the G(1) phase. The proportion of cells in the G(1) phase was significantly increased from 58.51% to 75.92%, and in the S and G(2)/M phases decreased significantly from 20.05% to 12.60%, and from 21.44% to 11.48%, respectively, as compared with those of the control groups. PC-3/p14ARF cells that underwent 5-Fu treatment had significantly greater G(2)/M phase accumulation, from 11.48% to 53.47%. The apoptopic index was increased in PC-3/p14ARF cells from 3.64% to 19.62%. The MTT assay showed p14ARF-expressing cells were significantly more sensitive to 5-Fu (0.01 - 10 mg/L) than those devoid of p14ARF expression (P < 0.01). Western blotting showed p14ARF upregulates p53 expression. CONCLUSION: Combined use of p14ARF gene and 5-Fu acts synergistically to inhibit pancreatic cancer cell proliferation, suggesting a new anticancer strategy.

Fluorouracil↗

[Screening for proteins interacting with novel gene AngRem104 in the adult human kidney cDNA library by yeast two hybrid system].

OBJECTIVE: To screen for proteins interacting with novel gene AngRem104. METHODS: The yeast strain AH109 was transformed with AngRem104-pGBKT7/c-myc, and yeast-mating was utilized to screen for interacting proteins with AngRem104 in pretransformed human kidney cDNA library. RESULTS: AngRem104 protein was expressed and there was no self-activation and toxicity in AH109. Seven proteins that interacted with AngRem104, including eukaryotic translation elongation factor 1 alpha 1, glucocorticoid receptor AF-1 specific elongation factor, beta 2-microglobulin, BBS2 and four of cell metabolism related proteins, were identified. CONCLUSION: The novel gene AngRem104 may interact with the proteins, which may interfere with cell metabolism, disturb the balance between transcription factors, or may be involved in some immunity related and hereditary diseases. This investigation provides functional clues for further exploration of the novel gene, AngRem104.

DNA, Complementary↗

Determination of selenium concentration of rice in china and effect of fertilization of selenite and selenate on selenium content of rice.

A method of hydride generation atomic fluorescence spectrometry was applied to the determination of the selenium concentration of regular polished rice in China and selenium-enriched polished rice obtained by foliar application of selenium-enriched fertilizer in the forms of selenite and selenate. The average selenium content of regular rice was 0.025 +/- 0.011 microg g(-)(1). On the basis of a daily dietary rice intake of 300-500 g suggested by the China Nutrition Society, the total selenium intake from regular rice was calculated to be 7.5-12.5 microg per person per day for an adult. The selenium contents of rice were significantly increased to 0.471-0.640 microg g(-)(1) by foliar application of selenium-enriched fertilizer at rate of 20 g of Se ha(-)(1) in the forms of sodium selenite and sodium selenate. The selenium content of rice by application of a fertilizer of selenate was 35.9% higher than that by a fertilizer of selenite, which showed that Se-enriched fertilizer in selenate exhibited greater efficiency in increasing Se content in rice products. The Se-enriched rice products can increase daily Se intake on average by 100-200 microg of Se per day by the consumption of 400 g of rice products if the Se level of rice products is controlled at 0.3-0.5 microg of Se g(-)(1). Because rice is a staple food in China, selenium-enriched rice obtained by bioenrichment of selenium to increase the Se content of rice could be a good selenium source for the population in selenium-deficient regions.

China↗

[Inhibition of proliferation of human vascular smooth muscle cells by overexpression of p21 gene].

OBJECTIVE: To observe the apoptosis of human vascular smooth muscle cells (HVSMCs) transfected with p21 gene and investigate its potential mechanism. METHODS: An adenoviral expression vector with full-length cDNA of p21 gene insert (Ad-p21) was constructed and transfected into HVSMC. A mock vector, pAdeno-X-lac Z constructed with the same method, was transfected into HVSMCs as control. Western blotting and DS-PAGE were used to detect the expression of p21 gene. Fluorescence staining was used to observe the changes in nuclei of apoptotic cells and calculate the cell survival rate. Expression of tissue transglutaminase (tTG) in HVSMC was examined by DIG-marked probe. RESULTS: Fluorescence staining showed marked fragmentation of nucleus and pyknosis of chromatin in pAdeno-X-p21 transfected cells. The expression of tTG was at a higher level in pAdeno-X-p21 transfected cells than in normal cells and pAdeno-X-lac transfected HVSMCs. CONCLUSION: Overexpression of p21 gene inhibits the proliferation of HVSMC through apoptosis induced by p21 which may relate with overexpression of tTG.

Apoptosis↗

[Regional intra-arterial infusion chemotherapy for pancreatic cancer: an experimental study].

OBJECTIVE: To verify the feasibility of regional intra-arterial infusion chemotherapy with gemcitabine for the treatment of locally advanced pancreatic cancer. METHODS: 10 Beagle dogs were divided into two groups: the experimental group and the control group. In the experimental group, gemcitabine (45 mg/kg) were infused via a transfemorally placed catheter into the celiac axis and superior mesenteric artery. IAC was given over 30 min with the help of DSA. In the control group, chemotherapy was performed via peripheral veins with the same dosage as the experimental group. Blood samples, heart, lung, liver, kidney, pancreas and parapancreatic tissues were obtained for drug concentration determination and pathological examination. RESULTS: The serum concentration of experimental group were significantly higher than those of the control group 2 hr, 4 hr and 8 hr after treatment (P < 0.05). Area under curve after dosage-based calibration in experimental group was much higher than that in control group (P < 0.05). The mean retention time of the drug in the animal body was significantly longer in experimental group than in control group. Pancreatic gemcitabine titer in experimental group was significantly higher than that in control group 4 hr and 8 hr after drug administration. There were a large number of red blood cells in the renal glomerulus and tubules, congestion and hemorrahge in the pulmonary capillaries and myocardium in the control group according to pathological examinations. However, infiltration of neutrophilic white blood cells, hemorrahge and fibrinous exudation were present in parapancreatic tissues which were absent in the group. CONCLUSION: Regional intra-arterial infusion chemotherapy with gemcitabine could increase serum and pancreatic drug concentration, prolongs retention time of the drug in the animal body, and is feasible in the treatment of pancreatic cancer.

Animals↗

Large-scale purification and characterization of malaria vaccine candidate antigen Pvs25H for use in clinical trials.

The budding yeast Saccharomyces cerevisiae has been used to express the recombinant protein Pvs25H, currently the only candidate transmission-blocking vaccine against Plasmodium vivax malaria. This molecule contains four epidermal growth factor-like domains and is expressed as at least two stable monomeric forms with different physicochemical properties. Pvs25H-A is apparently homogeneous and seems to have a correct disulfide bond structure. By contrast, Pvs25H-B is produced as a heterogeneous population of molecules, some of which are associated with an as yet unidentified chromophore, and it contains both internal and N-terminal cleavages. We report here a procedure for successfully separating these two forms with a process suitable for clinical production of this antigen.

Amino Acid Sequence↗

In vitro studies with recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1): production and activity of an AMA1 vaccine and generation of a multiallelic response.

Apical membrane antigen 1 (AMA1) is regarded as a leading malaria blood-stage vaccine candidate. While the overall structure of AMA1 is conserved in Plasmodium spp., numerous AMA1 allelic variants of P. falciparum have been described. The effect of AMA1 allelic diversity on the ability of a recombinant AMA1 vaccine to protect against human infection by different P. falciparum strains is unknown. We characterize two allelic forms of AMA1 that were both produced in Pichia pastoris at a sufficient economy of scale to be usable for clinical vaccine studies. Both proteins were used to immunize rabbits, singly and in combination, in order to evaluate their immunogenicity and the ability of elicited antibodies to block the growth of different P. falciparum clones. Both antigens, when used alone, elicited high homologous anti-AMA1 titers, with reduced strain cross-reactivity. Similarly, sera from rabbits immunized with a single antigen were capable of blocking the growth of homologous parasite strains at levels theoretically sufficient to clear parasite infections. However, heterologous inhibition was significantly reduced, providing experimental evidence that AMA1 allelic diversity is a result of immune pressure. Encouragingly, rabbits immunized with a combination of both antigens exhibited titers and levels of parasite inhibition as good as those of the single-antigen-immunized rabbits for each of the homologous parasite lines, and consequently exhibited a broadening of allelic diversity coverage.

Alleles↗

[The study of pro-nucleating activity on 33.5 x 10(3) vesicular protein in bile].

OBJECTIVE: To evaluate the pro-nucleating activity in 33.5 x 10(3) vesicular protein. METHODS: The model biles were established according Kibe and Zhu. The pro-nucleating activity of 33.5 x 10(3) vesicular protein were examined by polarized light microscopy. The protein and its enzymatic deglycosylation and proteolysis fractions nucleation promoting activity were detected by cholesterol crystal growth assay. RESULTS: 33.5 x 10(3) vesicular protein displayed apparent potency of pro-nucleation with activity of 0.310, and derived crystal growth curve indices It, Ig, Ic were presented as 0.57, 1.52, 1.63 respectively, but after treated by N-glycanase enzyme and pronase, no promoting activity were found. CONCLUSION: The 33.5 x 10(3) vesicular protein may be involved in the nucleation process of gallstone formation, which is regulated by its peptide and sugar chain.

Bile↗

[Examining consecutively serum leptin levels in normal pregnant and pregnancy-induced hypertension women].

OBJECTIVE: To detect successsively serum leptin levels in normal, pregnancy-induced hypertension (PIH) pregnant women. METHODS: Levels of serum leptin were measured in the 16-20, 24-28, 32-36 weeks of gestation, at the delivery time in 50 healthy, 14 PIH pregnant women and their newborns and in 40 healthy non-pregnant women by Immuno-radioassay method. Serum leptin levels were correlated with body weight, body mass index (BMI), blood pressure and placental weight. RESULTS: (1) The serum leptin levels were increased gradually during the normal (14.1 +/- 2.2)-(25.4 +/- 2.7) micro g/L and the PIH pregnancy [(13.4 +/- 3.0)-(21.4 +/- 3.7)] micro g/L, especially in the PIH women. It was found that leptin concentrations rose markedly from 28 to 36 weeks of gestation, but increased slightly before the 28 weeks of gestation and after the 36 weeks of gestation in normals, and in contrast to the normal pregnancy, consistently higher until to the delivery time in the PIH. (2) The positive correlations were significant between the levels of serum leptin with their body weight and BMI in the normal pregnant and non-pregnant women (r = 0.478-0.639, P < 0.05 or P < 0.01), but not significant in the PIH pregnant (r = 0.035-0.379, P > 0.05). (3) The positive correlations were significant between the serum leptin concentrations and the systolic blood pressure, diastolic blood pressure and mean artery pressure in the PIH women after 20 weeks of gestation (r = 0.639-0.852, P < 0.05), but not significant in the normal pregnant, the PIH before 20 weeks of gestation and the non-pregnant women (r = 0.113-0.498, P > 0.05). (4) Before the delivery time, the positive correlation between the serum leptin concentrations of the pregnant women and that of the newborns was not significant, and also not significant between the puerperas' serum leptin levels and the placental weight in the normal pregnant (r = 0.132, 0.097, P > 0.05). But it was interesting that significant positive correlation was found between the puerperas' serum leptin concentrations and the cord serum leptin levels (r = 0.792, P < 0.01) and significant negative correlation was detected between the puerperas' serum leptin levels and the placental weight in the PIH women (r = -0.819, P < 0.01). (5) The leptin levels of cord blood were positively correlated with the body weight and BMI of newborns in both of the normal and PIH pregnancy (r = 0.520-0.655, P < 0.05 or P < 0.01). CONCLUSION: The characteristic change of serum leptin levels and correlations between the serum leptin concentrations and the related pregnant signs was different in normal and PIH pregnancy.

Blood Pressure↗