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Biomedical subjects

Yang Zhao

Publications and source records attributed to Yang Zhao.

At least 37 records · Page 2Linked to original sources

Antioxidant constituents in the fruits of Luffa cylindrica (L.) Roem.

Hydrophilic antioxidant constituents in the fruits of the vegetable Luffa cylindrica (L.) Roem (sponge gourds) were separated by an antioxidant-guided assay to yield eight compounds: p-coumaric acid (1), 1-O-feruloyl-beta-D-glucose (2), 1-O-p-coumaroyl-beta-D-glucose (3), 1-O-caffeoyl-beta-D-glucose (4), 1-O-(4-hydroxybenzoyl)glucose (5), diosmetin-7-O-beta-D-glucuronide methyl ester (6), apigenin-7-O-beta-D-glucuronide methyl ester (7), and luteolin-7-O-beta-D-glucuronide methyl ester (8). The eight compounds were isolated by high-speed countercurrent chromatography and identified by electrospray ionization-mass spectrometry and NMR analysis, and the antioxidant activity was evaluated by the radical scavenging effect on the 1,1-diphenyl-2-picrylhydrazyl radical. High-performance liquid chromatography analysis showed that a total amount of the eight compounds in the dried gourds without skin was about 1%. The results demonstrate that the consumption of sponge gourds can supply some antioxidant constituents to human body.

Antioxidants↗

A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells.

Traditionally, undifferentiated human embryonic stem cells (hESCs) are maintained on mouse embryonic fibroblast (MEF) cells or on matrigel with an MEF-conditioned medium (CM), which hampers the clinical applications of hESCs due to the contamination by animal pathogens. Here we report a novel chemical-defined medium using DMEM/F12 supplemented with N2, B27, and basic fibroblast growth factor (bFGF) [termed NBF]. This medium can support prolonged self-renewal of hESCs. hESCs cultured in NBF maintain an undifferentiated state and normal karyotype, are able to form embryoid bodies in vitro, and differentiate into three germ layers and extraembryonic cells. Furthermore, we find that hESCs cultured in NBF possess a low apoptosis rate and a high proliferation rate compared with those cultured in MEF-CM. Our findings provide a novel, simplified chemical-defined culture medium suitable for further therapeutic applications and developmental studies of hESCs.

Apoptosis↗

Several acidic amino acids in the N-domain of insulin-like growth factor-binding protein-5 are important for its transactivation activity.

Insulin-like growth factor-binding protein (IGFBP)-5 is a secreted protein that binds to IGFs and modulates IGF actions. IGFBP-5 is also found in the nuclei of cultured cells and has transactivation activity. Here we report the nuclear localization of endogenous IGFBP-5 in mouse embryonic skeletal cells. Chromatin immunoprecipitation experiments indicated that IGFBP-5 interacts with the nuclear histone-DNA complex. Using a series of deletion mutants, the transactivation domain of IGFBP-5 was mapped to its N-terminal region. Intriguingly, the transactivation activity of IGFBP-5 is masked by negative regulatory elements located in the L- and C-domains. Among the other IGFBPs, the N-domains of IGFBP-2 and -3 also had strong transactivation activity, whereas those of IGFBP-1 and -6 had no activity. The IGFBP-4 N-domain had modest activity. Sequence analysis revealed several amino acids in the IGFBP-5 N-domain that are not present in IGFBP-1. The activities of mutants in which these residues were changed to the corresponding IGFBP-1 sequence were determined. Mutations that changed acidic residues to neutral residues (e.g. E8A, D11S, E12A, E30S/P31A, E43L, and E52A) or a polar to a basic residue (e.g. Q56R) significantly reduced transactivation activity. The E8A/D11S/E12A triple mutant and E52A/Q56R double mutants showed further reduced activity. The combinatory mutants had essentially no transactivation activity. Taken together, our results indicate that there are several conserved residues in the IGFBP-5 N-terminal region that are critical for transactivation and that IGFBP-2 and -3 also have strong transactivation activity in their N-domains.

Amino Acid Sequence↗

[Estimation on gene-environment interaction in the partial case-control study].

OBJECTIVE: To introduce the approaches for estimating gene-environment interaction based on partial case-control studies. METHODS: The effects of logistic model and log-linear model for estimating the main effects and gene-environment interaction effect were estimated by means of maximum likelihood methods in traditional case-control studies, case-only studies and partial case-control studies, respectively. An example was also illustrated. RESULTS: In traditional case-control study with complete data, the results of logistic model and log-linear model were equivalent. In case-only study without any information about controls, the logistic model can also efficiently estimate gene-environment interaction. In partial case-control study, environmental information was collected from all of the cases and controls, while genetic information was only collected from cases. For this case-control study with incomplete data, a suitable parameterized log-linear model could simultaneously and efficiently estimate the main effect of environment and gene-environment interaction, whereas the logistic model could not. CONCLUSION: For a partial case-control study, log-linear model could estimate not only the main effect of environment but also gene-environment interaction. If genotype and exposure were independent, estimators from partial case-control were as precisely as those from complete-data case-control studies.

Case-Control Studies↗

[Introduction on "case-sibling control design"].

OBJECTIVE: To introduce the design and statistical methods of case-sibling control design and to analyze the published data. METHODS: Data from an association study between the coronary heart disease and methylenetetrahydrofolate reductase gene C677T polymorphism was analyzed by the sib transmission/disequibrium test (s-TDT) and the sibship disequilibrium (SDT) methods. RESULTS: Using s-TDT method, Z value was 0.27 with P > 0.05. The result of SDT method showed that chi-square was 0.31 with 1 df, P > 0.05. All results suggested that neither s-TDT nor SDT showed significant difference between the transmitted and untransmitted methylenetetrahydrofolate reductase gene C677T allele distributions. CONCLUSION: Case-sibling control design might avoid population stratification by using siblings as controls thus might be used to test association and linkage between genes and disease.

Case-Control Studies↗

[Clinical value of adjuvant therapy with estrogen for postpartum hemorrhage].

OBJECTIVE: To investigate the clinical efficacy of estrogen in management of postpartum hemorrhage due to uterine atony. METHODS: Totalling 112 puerperants with postpartum hemorrhage due to uterine atony were randomly assigned into 2 groups and received routine managements for uterine atony such as uterine massage and uterotonics administration. The puerperants in one group (n=52) was treated with 4 mg estradiol benzoate injected intramuscularly, and the amount of blood loss 2 h after delivery and between 2 and 24 h after delivery was recorded. RESULTS: There were significant differences in vaginal blood loss at 2 h after delivery between the 2 groups (P<0.05). The puerperants with estrodiol benzoate treatment had blood loss of 589.6-/+226.4 ml at 2 h and 110.8-/+76.2 ml within 2-24 h after delivery, which were both less than those in the control group (864.5-/+359.5 ml and 161.5-/+98.3 ml, respectively). Postpartum hysterectomy was performed in 3 cases of the control group while none in estradiol benzoate-treated group. In the mothers and neonates, no major adverse effects were observed. CONCLUSION: Estrogen shows cooperative efficacy with uterotonics in stimulating uterine contraction for managements of postpartum hemorrhage due to uterine atony, and can be of value in clinical application.

Adult↗

[Analysis of regulatory regions of mammalian DMRT1 genes].

Dmrt1 gene is the first sex differentiation gene found conserved across animal phyla. It plays an important role in mammalian sexual differentiation. Sequence analysis of mammalian dmrt1 5' and 3' flanking regions showed that there were three and seven conserved regions (>60% homology), respectively. Dmrt1 promoter, 3' flanking region and coding sequence were amplified, cloned into expression vectors and transfected into both COS-7 and ST cells. Results indicated that both 5' and 3' flanking sequences could direct the expression of reporter gene gfp and dmrt1. However there was clearly a difference in expression efficiency between different cells. These results indicated that regulation of dmrt1 expression may be cell-specific and complex regulatory mechanism may be involved in dmrt1 expression.

Animals↗

Elevated risk of colorectal cancer associated with the AA genotype of the cyclin D1 A870G polymorphism in an Indian population.

PURPOSE: To investigate whether the common cyclin D1 (CCND1) A870G polymorphism is a risk factor for colorectal cancer (CRC) in an Indian population. METHODS: In this study, 301 newly diagnosed CRC patients and 291 healthy control subjects were genotyped by the PCR-RFLP method. Genotype frequencies were compared between cases and controls, and the association of genotypes with CRC was studied. RESULTS: The CCND1 870 A allele was more frequently observed in CRC patients than controls (0.63 vs. 0.56, P=0.01), and after adjustment for age, sex, smoking habits, family history, family income and the consumption of meat, fish, vegetables and fruit, an increased risk was observed for the AA genotype compared to the GG+AG genotype (OR=1.56; 95% CI: 1.10-2.21). The increased risk were also found for colon (OR=1.96; 95% CI: 1.08-3.57) and rectal cancer (OR=1.51; 95% CI: 1.04-2.19). No correlation was observed between genotypes and age of diagnosis of CRC (49.9, 48.7 and 49.4 years for the GG, AG and AA genotypes, respectively; P=0.84). Multivariate analysis also revealed a stronger positive association with the AA genotype among patients with high meat intake (OR=2.67; 95% CI: 1.29-5.51), and particularly significant inverse associations with the GG+AG genotypes were also found for those with high vegetable consumption (OR=0.46; 95% CI: 0.27-0.79 of 2-3 servings/day, and OR=0.31; 95% CI: 0.18-0.53 for >3 servings/day) and fish intake (OR=0.48; 95% CI: 0.28-0.82). CONCLUSION: These data support the hypothesis that the CCND1 A870G polymorphism may increase the risk of CRC in our Indian population.

Adult↗

S-adenosyl-L-homocysteine hydrolase inactivation curtails ovalbumin-induced immune responses.

The reversible S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitor methyl 4-(adenin-9-yl)-2-hydroxybutanoate (DZ2002) suppresses macrophage activation and function. The effects of DZ2002 on T cell function, however, are still unclear. Here, we examined whether DZ2002 alters type 1 helper T cell (Th1) and/or type 2 helper T cell (Th2) immune responses, and whether these effects are associated with both the inhibition of AdoHcy hydrolase and intracellular elevation of endogenous AdoHcy. Male C57BL/6 mice immunized with ovalbumin (OVA) were treated with DZ2002 (1, 5, and 25 mg/kg/day) after which lymphocyte proliferation, cytokine production, and IgG responses to OVA were monitored. Administration of DZ2002 dose dependently suppressed OVA-specific lymphocyte proliferation and anti-OVA IgG production compared with controls. Interleukin (IL)-2 and interferon (IFN)-gamma as well as anti-OVA IgG2a and IgG3, indicators of Th1 immune responses, were markedly decreased in mice treated with DZ2002, whereas IL-4 and anti-OVA IgG1, indicators of Th2 immune responses, were only mildly suppressed. AdoHcy hydrolase activity in spleens of DZ2002-treated mice was substantially blocked, and not surprisingly, AdoHcy levels were significantly elevated compared with controls. Finally, similar immunosuppressive effects were also observed in mice treated with AdoHcy. These data strongly indicate that DZ2002 suppresses antigen-induced specific immune responses, particularly Th1 responses, through inhibition of AdoHcy hydrolase and elevation of endogenous AdoHcy.

Adenine↗

Synthesis and activity of an octapeptide inhibitor designed for SARS coronavirus main proteinase.

The outbreak of SARS, a life-threatening disease, has spread over many countries around the world. So far there is no effective drug for the treatment of SARS. Stimulated by the binding mechanism of SARS-CoV Mpro with the octapeptide AVLQSGFR reported recently as well as the "Chou's distorted key" theory, we synthesized the octapeptide AVLQSGFR for conducting various biochemical experiments to investigate the antiviral potential of the octapeptide against SARS coronavirus (BJ-01). The results demonstrate that, compared with other compounds reported so far, AVLQSGFR is the most active in inhibiting replication of the SARS coronavirus, and that no detectable toxicity is observed on Vero cells under the condition of experimental concentration.

Amino Acid Sequence↗

Effects of tributyltin, benzo[a]pyrene, and their mixture on antioxidant defense systems in Sebastiscus marmoratus.

It has been reported that there is a metabolic interaction between tributyltin (TBT), an organometal used as an antifouling biocide, and benzo[a]pyrene (BaP), a widespread carcinogenic polycyclic aromatic hydrocarbon. This study was therefore designed to examine the potential in vivo influence of TBT, BaP, and their mixture on hepatic antioxidant defense systems of Sebastiscus marmoratus, which were given a single ip injection of TBT (0.5, 1, 5, and 10mg/kg), BaP (0.5, 1, 5, and 10mg/kg), or both in combination (0.5, 1, 5, and 10mg/kg); control fish received olive oil vehicle only. Samples were collected for biochemical analysis after injection for 7 days. Cotreatment with BaP caused a significant inhibition of TBT-mediated malondialdehyde contents elevation. Cotreatment with TBT decreased BaP-mediated glutathione peroxidase activity induction. Cotreatment with TBT and BaP did not significantly alter the reduced glutathione levels, which were significantly induced by TBT or BaP alone. TBT-induced suppression of BaP bioactivation or BaP-induced stimulation of the phase II metabolism of TBT and its biliary excretion, both of which have been reported previously, could explain the observed antagonism. The results suggest that combined exposure of TBT and BaP increases the vulnerability of the fish to oxidative stress. BaP cotreatment decreased the induction of glutathione S-transferase (GST) activity by the lower dose of TBT, while cotreatment with TBT and BaP at the highest dose (10mg/kg) resulted in inhibition of the GST activity by 4.8-fold. The results suggest that these biomarkers should be interpreted with caution in biomonitoring studies. Combined effects of TBT and BaP exposure at environmental levels on these biomarkers should be further researched.

Animals↗

Molecular cloning, expression of Sox5 and its down-regulation of Dmrt1 transcription in zebrafish.

The doublesex and mab-3-related transcription factor 1 (Dmrt1) is the founding member of a family of DM domain genes, involved in gonadogenesis. Here we report the cloning of zebrafish Sox5 and use real time PCR to show that its expression increases while expression of Dmrt1 decreases during embryogenesis. Characterization of the proximal promoter of zebrafish Dmrt1 revealed two positive and two negative regulatory regions and a Sox5-binding site. Co-transfection of dmrt1 (with or without the Sox-binding site), driving an EGFP reporter and Sox5 showed further that Sox5 bound the Dmrt1 promoter and inhibited Dmrt1 expression. This antagonistic partnership between Dmrt1 and Sox5 suggests a potential transcriptional regulatory mechanism for Dmrt1 in early embryogenesis.

Amino Acid Sequence↗

Colloidal subwavelength nanostructures for antireflection optical coatings.

A two-dimensional (2D) subwavelength nanostructure for antireflection coating is fabricated upon a transparent substrate. Self-assembled 2D colloidal crystals are used as a nanoscale composite material with controlled thickness and low refractive index. The feature size of the structure is approximately 105 nm. The structure is used for antireflection coating, and the measured reflectivity of a glass substrate is reduced to 0.3%. Enhanced transmission through the substrate is also observed.

Journal Article↗

Noggin and bFGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers.

Human embryonic stem (hES) cells are typically maintained on mouse embryonic fibroblast (MEF) feeders or with MEF-conditioned medium. However, these xenosupport systems greatly limit the therapeutic applications of hES cells because of the risk of cross-transfer of animal pathogens. Here we showed that the bone morphogenetic protein antagonist noggin is critical in preventing differentiation of hES cells in culture. Furthermore, we found that the combination of noggin and basic fibroblast growth factor (bFGF) was sufficient to maintain the prolonged growth of hES cells while retaining all hES cell features. Since both noggin and bFGF are expressed in MEF, our findings suggest that they may be important factors secreted by MEF for maintaining undifferentiated pluripotent hES cells. Our data provide new insight into the mechanism how hES cell self-renewal is regulated. The newly developed feeder-free culture system will provide a more reliable alternative for future therapeutic applications of hES cells.

Animals↗

Interactions of nanosized Al2O3 and ZnO with poly(ethylene oxide)-NaSCN polymer electrolytes.

The effect of nanosized Al2O3/ZnO fillers on the interactions in PEO-NaSCN polymer electrolytes has been studied by FT-IR, XRD, and DTA measurements. The experimental results are discussed according to the grain boundary effect, the principle of Lewis acid-base, and epitaxial effect. It is shown that the hard Lewis acid centers on the surface of Al2O3 exhibit strong interactions with ether oxygens in PEO, even with ether oxygens that coordinated to Na+. Therefore, the modes of the interaction of Al2O3 with PEO-NaSCN electrolytes are dependent on the salt content. Al2O3 cannot influence the ionic association in P(EO)8NaSCN electrolyte, but do reduce significantly the solvating ability of PEO toward NaSCN in P(EO)60NaSCN electrolyte. However, NaSCN in P(EO)20NaSCN-30%Al2O3 nanocomposite appears as a state that resembles the situation of NaSCN in PEO amorphous phase. In contrast with Al2O3, the epitaxial effect of ZnO is not found in the interested systems where only weaker interaction is observed between ZnO and ether oxygen, and the modes of interaction of ZnO with PEO-NaSCN electrolytes are hardly related to the salt content. In addition, the soft Lewis acid groups on ZnO surface exhibit stronger complexation with SCN- in PEO-NaSCN electrolytes, and both can form the complex anion ZnO...SCN-.

Journal Article↗

FT-Raman spectroscopic evidences for the preferential solvation of sodium tetrafluorobrate in acetonitrile-based mixed solvents.

Solutions of sodium tetrafluorobrate in acetonitrile-dimethylformamide, and acetonitrile-dimethylsulfoxide mixtures have been studied by FT-Raman spectroscopy for three solvent compositions, respectively. New bands due to solvent molecules in the first solvation shell of Na(+) were detected in the region of the O=C--N deformation and CH(3) rocking mode for amide and of the S=O and C--S stretching modes for sulfoxide. The individual solvation numbers of sodium cation in different environment were deduced. In all the cases, it is found that the sodium ion was preferentially solvated by DMF or DMSO in respective binary solvents. This result was further supported by ab initio calculations.

Acetonitriles↗

Melanocyte-specific proteins are aberrantly trafficked in melanocytes of Hermansky-Pudlak syndrome-type 3.

Hermansky-Pudlak Syndrome-type 3 (HPS-3) is a relatively mild subtype of HPS with minimal cutaneous and ocular depigmentation. The HPS-3 gene encodes a novel protein of unknown function with a predicted molecular weight of 114 kd. To assess the role of the HPS3 protein in melanization, cultured melanocytes developed from HPS-3 patients were evaluated biochemically and histologically for activity and localization of melanocyte-specific proteins. Endogenous tyrosinase activity of HPS-3 melanocytes was substantial, but tyrosinase activity and melanin synthesis was suppressed in intact melanocytes. However, the level of suppression, as well as extent to which up-regulation by isobutylmethylxanthine and cholera toxin was muted, was less that in HPS-1 melanocytes. Ultrastructurally, HPS-3 melanocytes contained morphologically normal melanosomes, predominantly of stage I and II with minimal stage III and few stage IV melanosomes. Dihydroxyphenylalanine (DOPA) histochemistry demonstrated an increase in melanization of melanosomes. Unique to HPS-3 melanocytes were numerous DOPA-positive 50-nm vesicles and tubular elements present throughout the cell body and dendrites. Tyrosinase, tyrosinase-related protein-1 (Tyrp1), dopachrome tautomerase (Dct), and LAMP1 and 3 localization in HPS-3 melanocytes, as evaluated by immunocytochemistry and confocal microscopy, demonstrated a fine, floccular distribution in contrast to the coarse, granular distribution characteristic of control melanocytes. The localization profile of other proteins expressed by melanocytes (ie, Silver/Pmel17, Melan-A/MART-1, LAMP2, Rab 27, transferrin, c-kit, adaptin-3, and the HPS1 protein) appeared normal. These results suggest that a specific subset of melanocyte proteins are aberrantly trafficked throughout the HPS-3 melanocyte and may be responsible for the reduction in melanin synthesis.

Carrier Proteins↗

Melanocytes derived from patients with Hermansky-Pudlak Syndrome types 1, 2, and 3 have distinct defects in cargo trafficking.

Hermansky-Pudlak Syndrome (HPS) is a genetically heterogeneous disorder in which mutations in one of several genes interrupts biogenesis of melanosomes, platelet dense bodies, and lysosomes. Affected patients have oculocutaneous albinism, a bleeding diathesis, and sometimes develop granulomatous colitis or pulmonary fibrosis. In order to assess the role of HPS genes in melanosome biogenesis, melanocytes cultured from patients with HPS subtypes 1, 2, or 3 were assessed for the localization of various melanocyte proteins. Tyrosinase, Tyrp1, and Dct/Tyrp2 were atypically and distinctly expressed in HPS-1 and HPS-3 melanocytes, whereas only tyrosinase showed an atypical distribution in HPS-2 melanocytes. The HPS1 and AP3B1 (i.e., HPS-2) gene products showed no expression in HPS-1 and HPS-2 melanocytes, respectively, whereas HPS-3 melanocytes exhibited normal expression for both proteins. In normal human melanocytes, the HPS1 protein was expressed as an approximately 80 kDa molecule with both granular and reticular intracellular profiles. In HPS-1, lysosome associated membrane protein 1 (LAMP1), and LAMP3 were localized to abnormal large granules; in HPS-2, all LAMPs exhibited a normal granular expression; and in HPS-3, LAMP1, and LAMP3 exhibited a distinct less granular and more floccular pattern. In contrast, the expressions of Rab 27, transferrin, and cKit were unaffected in all three HPS genotypes. These data demonstrate that the three initially identified subtypes of human HPS exhibit distinct defects in the trafficking of various melanocyte-specific proteins.

Adaptor Protein Complex 3↗