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Biomedical subjects

Xiaobing Yi

Publications and source records attributed to Xiaobing Yi.

5 recordsLinked to original sources

LncRNA HAR1A in triple-negative breast cancer: mechanisms and the role of polymorphism rs 6089838 in susceptibility.

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly recognized as crucial regulators and potential biomarkers in triple-negative breast cancer (TNBC). This study examined the link between the rs6089838 polymorphism in HAR1A and TNBC susceptibility/progression and function. RESEARCH DESIGN AND METHODS: 197 TNBC patients and 185&#xa0;healthy controls were recruited. Rs6089838 genotyping and serum lncRNA HAR1A quantification were performed using qRT PCR. Survival was analyzed via KM and Cox regression.. Cellular proliferation, migration, and invasion were measured using CCK-8 and Transwell assays. RESULTS: The GG genotype significantly lowered TNBC risk versus the AA genotype (OR =0.393, p&#x2009;=&#x2009;0.002). GA/GG genotypes were associated with more favorable clinicopathological features. Serum lncRNA HAR1A was downregulated in TNBC patients (p&#x2009;<&#x2009;0.001) and was positively correlated with the protective G allele frequency (p&#x2009;<&#x2009;0.001). GA/GG carriers showed significantly longer overall survival than AA homozygotes (p&#x2009;<&#x2009;0.001). Functional studies confirmed that HAR1A overexpression via pcDNA3.1 suppressed proliferation, migration, and invasion in breast cancer cell lines. Conversely, siRNA-mediated lncRNA HAR1A knockdown enhanced these oncogenic traits. CONCLUSION: The G allele of HAR1A rs6089838 represents a protective variant against TNBC susceptibility and progression, likely through HAR1A's tumor-suppressive activity. This SNP may have potential as a biomarker for TNBC risk and prognosis assessment.

Humans↗

Gold nanoparticles: catalyst for the oxidation of NADH to NAD(+).

Nicotinamide adenine dinucleotide is an important coenzyme involved in the production of ATP, the fuel of energy, in every cell. It alternates between the oxidized form NAD(+) and the reduced form dihydronicotinamide adenine dinucleotide (NADH) and serves as a hydrogen and electron carrier in the cellular respiratory processes. In the present work, the catalytic effect of gold nanoparticles on the oxidization of NADH to NAD(+) was investigated. The addition of gold nanoparticles was found to quench the NADH fluorescence intensities but had no effect on the fluorescence lifetime. This suggested that the fluorescence quenching was not due to coupling with the excited state, but due to changing the ground state of NADH. The intensity of the 340 nm absorption band of NADH was found to decrease while that of the 260 nm band of NAD(+) was found to increase as the concentration of gold nanoparticles increased. This conversion reaction was further supported by nuclear magnetic resonance and mass spectroscopy. The effect of the addition of NADH was found to slightly red shift and increase the intensity of the surface plasmon absorption band of gold nanoparticles at 520 nm. This gives a strong support that the conversion of NADH to NAD(+) is occurring on the surface of the gold nanoparticles, i.e. NADH is surface catalyzed by the gold nanoparticles. The catalytic property of this important reaction might have important future applications in biological and medical fields.

Catalysis↗

Characterization of a human core-specific lysosomal {alpha}1,6-mannosidase involved in N-glycan catabolism.

In humans and rodents, the lysosomal catabolism of core Man(3)GlcNAc(2) N-glycan structures is catalyzed by the concerted action of several exoglycosidases, including a broad specificity lysosomal alpha-mannosidase (LysMan), core-specific alpha1,6-mannosidase, beta-mannosidase, and cleavage at the reducing terminus by a di-N-acetylchitobiase. We describe here the first cloning, expression, purification, and characterization of a novel human glycosylhydrolase family 38 alpha-mannosidase with catalytic characteristics similar to those established previously for the core-specific alpha1,6-mannosidase (acidic pH optimum, inhibition by swainsonine and 1,4-dideoxy-1,4-imino-d-mannitol, and stimulation by Co(2+) and Zn(2+)). Substrate specificity studies comparing the novel human alpha-mannosidase with human LysMan revealed that the former enzyme efficiently cleaved only the alpha1-6mannose residue from Man(3)GlcNAc but not Man(3)GlcNAc(2) or other larger high mannose oligosaccharides, indicating a requirement for chitobiase action before alpha1,6-mannosidase activity. In contrast, LysMan cleaved all of the alpha-linked mannose residues from high mannose oligosaccharides except the core alpha1-6mannose residue. alpha1,6-Mannosidase transcripts were ubiquitously expressed in human tissues, and expressed sequence tag searches identified homologous sequences in murine, porcine, and canine databases. No expressed sequence tags were identified for bovine alpha1,6-mannosidase, despite the identification of two sequence homologs in the bovine genome. The lack of conservation in 5'-flanking sequences for the bovine alpha1,6-mannosidase genes may lead to defective transcription similar to transcription defects in the bovine chitobiase gene. These results suggest that the chitobiase and alpha1,6-mannosidase function in tandem for mammalian lysosomal N-glycan catabolism.

Acetylglucosaminidase↗

Glycosidic torsional motions in a bicelle-associated disaccharide from residual dipolar couplings.

An analysis of torsional motions about glycosidic bonds in a disaccharide is undertaken using residual dipolar coupling measurements and selective immobilization of the reducing end sugar to provide a suitable motional reference. The immobilization is accomplished by using the short chain of an alkyl glycoside to anchor the disaccharide to a bilayer medium aligned in magnetic field. Motions about the beta-(1-4) linkage of the n-butyl-4-O-beta-d-galactopyranosyl-alpha-d-mannopyranoside are shown to be substantial (+/-40 degrees ) and in good agreement with predictions of a fully solvated molecular dynamics simulation.

Carbohydrate Conformation↗

CONDORR--CONstrained Dynamics of Rigid Residues: a molecular dynamics program for constrained molecules.

A computer program CONDORR (CONstrained Dynamics of Rigid Residues) was developed for molecular dynamics simulations of large and/or constrained molecular systems, particularly carbohydrates. CONDORR efficiently calculates molecular trajectories on the basis of 2D or 3D potential energy maps, and can generate such maps based on a simple force field. The simulations involve three translational and three rotational degrees of freedom for each rigid, asymmetrical residue in the model. Total energy and angular momentum are conserved when no stochastic or external forces are applied to the model, if the time step is kept sufficiently short. Application of Langevin dynamics allows longer time steps, providing efficient exploration of conformational space. The utility of CONDORR was demonstrated by application to a constrained polysaccharide model and to the calculation of residual dipolar couplings for a disaccharide. [Figure: see text]. Molecular models (bottom) are created by cloning rigid residue archetypes (top) and joining them together. As defined here, the archetypes AX, HM and BG respectively correspond to an alpha-D-Xyl p residue, a hydroxymethyl group, and a beta-D-Glc p residue lacking O6, H6a and H6b. Each archetype contains atoms (indicated by boxes) that can be shared with other archetypes to form a linked structure. For example, the glycosidic link between the two D-Glc p residues is established by specifying that O1 of the nonreducing beta-D-Glc p (BG) residue (2) is identical to O4 of the reducing Glc p (BG) residue (1). The coordinates of the two residues are adjusted so as to superimpose these two (nominally distinct) atoms. Flexible hydroxymethyl (HM) groups (3 and 4) are treated as separate residues, and the torsional angles (normally indicated by the symbol omega) that define their geometric relationships to the pyranosyl rings of the BG residues are specified as psi3 and psi4, respectively. The torsional angles phi3 and phi4, defined solely to maintain the orientation of the geminal H-atoms of the hydroxymethyl group, are not shown. (See text.). The illustrated trisaccharide is thus specified as a collection of 5 residues which are represented by 3 archetypes. Models of the disaccharide cellobiose (beta-D-Glc p-(1-->4)-D-Glc p) must include residues 1 and 2, but the hydroxymethyl groups (residues 3 and 4) can also be explicitly included in this model

Carbohydrates↗