Biomedical subjects

Jinfeng Zhang

Publications and source records attributed to Jinfeng Zhang.

7 recordsLinked to original sources

PubMed2026

NR3C1 Modulates Wnt Signalling to Influence the Invasiveness and Immune Features of Nonfunctioning Invasive Pituitary Adenomas.

Pituitary adenomas (PAs) are common intracranial tumours, and invasiveness in nonfunctioning invasive pituitary adenomas (NIPAs) predicts poor prognosis. The molecular mechanisms driving this phenotype remain unclear. This study explored the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in NIPA invasiveness and its regulation of Wnt signalling. mRNA expression profiles of 32 PA samples were generated by RNA-seq, and proteomic data from 19 samples were obtained by mass spectrometry. Immune-related differentially expressed genes (DEGs) were retrieved from GeneCards. Weighted gene coexpression network analysis identified modules and hub genes linked to invasiveness, while machine learning methods (support vector machine, LASSO, random forest) prioritised key genes. Gene set enrichment analysis (GSEA) assessed pathways associated with candidate gene expression. NR3C1 expression and function were validated by immunohistochemistry, Western blotting and invasion assays. Integration of transcriptomic, proteomic and immune-related datasets yielded 11 overlapping genes, with NR3C1 emerging as the top candidate. NR3C1 was significantly upregulated in NIPAs and demonstrated good discriminatory power by ROC analysis. GSEA associated high NR3C1 expression with Wnt pathway activation. Functional experiments confirmed that NR3C1 overexpression enhances the invasive capacity of PA cells. NR3C1 promotes the invasive phenotype of NIPAs by activating Wnt signalling. These findings suggest NR3C1 as a potential biomarker and therapeutic target for invasive pituitary adenomas.

Humans↗

PubMed2007

Monte Carlo sampling of near-native structures of proteins with applications.

Since a protein's dynamic fluctuation inside cells affects the protein's biological properties, we present a novel method to study the ensemble of near-native structures (NNS) of proteins, namely, the conformations that are very similar to the experimentally determined native structure. We show that this method enables us to (i) quantify the difficulty of predicting a protein's structure, (ii) choose appropriate simplified representations of protein structures, and (iii) assess the effectiveness of knowledge-based potential functions. We found that well-designed simple representations of protein structures are likely as accurate as those more complex ones for certain potential functions. We also found that the widely used contact potential functions stabilize NNS poorly, whereas potential functions incorporating local structure information significantly increase the stability of NNS.

Computer Simulation↗

PubMed2006

On side-chain conformational entropy of proteins.

The role of side-chain entropy (SCE) in protein folding has long been speculated about but is still not fully understood. Utilizing a newly developed Monte Carlo method, we conducted a systematic investigation of how the SCE relates to the size of the protein and how it differs among a protein's X-ray, NMR, and decoy structures. We estimated the SCE for a set of 675 nonhomologous proteins, and observed that there is a significant SCE for both exposed and buried residues for all these proteins-the contribution of buried residues approaches approximately 40% of the overall SCE. Furthermore, the SCE can be quite different for structures with similar compactness or even similar conformations. As a striking example, we found that proteins' X-ray structures appear to pack more "cleverly" than their NMR or decoy counterparts in the sense of retaining higher SCE while achieving comparable compactness, which suggests that the SCE plays an important role in favouring native protein structures. By including a SCE term in a simple free energy function, we can significantly improve the discrimination of native protein structures from decoys.

Algorithms↗

PubMed2006

Empirical potential function for simplified protein models: combining contact and local sequence-structure descriptors.

An effective potential function is critical for protein structure prediction and folding simulation. Simplified protein models such as those requiring only Calpha or backbone atoms are attractive because they enable efficient search of the conformational space. We show residue-specific reduced discrete-state models can represent the backbone conformations of proteins with small RMSD values. However, no potential functions exist that are designed for such simplified protein models. In this study, we develop optimal potential functions by combining contact interaction descriptors and local sequence-structure descriptors. The form of the potential function is a weighted linear sum of all descriptors, and the optimal weight coefficients are obtained through optimization using both native and decoy structures. The performance of the potential function in a test of discriminating native protein structures from decoys is evaluated using several benchmark decoy sets. Our potential function requiring only backbone atoms or Calpha atoms have comparable or better performance than several residue-based potential functions that require additional coordinates of side-chain centers or coordinates of all side-chain atoms. By reducing the residue alphabets down to size 10 for contact descriptors, the performance of the potential function can be further improved. Our results also suggest that local sequence-structure correlation may play important role in reducing the entropic cost of protein folding.

Amino Acid Sequence↗

PubMed2005

Quantitative determination of atractylenolide III in rat plasma by liquid chromatography electrospray ionization mass spectrometry.

Atractylenolide III is a major active component in Atractylodes macrocephala. This paper describes a simple, rapid, specific and sensitive method for the quantification of atractylenolide III in rat plasma using a liquid-liquid extraction procedure followed by liquid chromatography mass spectrometric (LC-MS) analysis. A Kromasil 3.5 microm C(18) column (150 mm x 2.00 mm) was used as the analytical column. Linear detection responses were obtained for atractylenolide III concentration ranging from 5 to 500 ng L(-1). The precision and accuracy data, based on intra-day and inter-day variations over 5 days were within 10.29%. The lower limit of quantitation for atractylenolide III was 5 ng mL(-1), using 0.1 mL plasma for extraction and its recoveries were greater than 85% at the low, medium and high concentrations. The method has been successfully applied to a pharmacokinetic study in rats after an oral administration of atractylenolide III with a dose of 20.0 mg kg(-1). With the lower limits of quantification at 5 ng mL(-1) for atractylenolide III, this method was proved to be sensitive enough for the pharmacokinetics study of atractylenolide III.

Animals↗

PubMed2004

Importance of chirality and reduced flexibility of protein side chains: a study with square and tetrahedral lattice models.

Side chains of amino acid residues are the determining factor that distinguishes proteins from other unstable chain polymers. In simple models they are often represented implicitly (e.g., by spin states) or simplified as one atom. Here we study side chain effects using two-dimensional square lattice and three-dimensional tetrahedral lattice models, with explicitly constructed side chains formed by two atoms of different chirality and flexibility. We distinguish effects due to chirality and effects due to side chain flexibilities, since residues in proteins are L residues, and their side chains adopt different rotameric states. For short chains, we enumerate exhaustively all possible conformations. For long chains, we sample effectively rare events such as compact conformations and obtain complete pictures of ensemble properties of conformations of these models at all compactness region. This is made possible by using sequential Monte Carlo techniques based on chain growth method. Our results show that both chirality and reduced side chain flexibility lower the folding entropy significantly for globally compact conformations, suggesting that they are important properties of residues to ensure fast folding and stable native structure. This corresponds well with our finding that natural amino acid residues have reduced effective flexibility, as evidenced by statistical analysis of rotamer libraries and side chain rotatable bonds. We further develop a method calculating the exact side chain entropy for a given backbone structure. We show that simple rotamer counting underestimates side chain entropy significantly for both extended and near maximally compact conformations. We find that side chain entropy does not always correlate well with main chain packing. With explicit side chains, extended backbones do not have the largest side chain entropy. Among compact backbones with maximum side chain entropy, helical structures emerge as the dominating configurations. Our results suggest that side chain entropy may be an important factor contributing to the formation of alpha helices for compact conformations.

Computer Simulation↗

PubMed2002

Study on the accuracy of automated hematology analyzers in Shanghai.

UNLABELLED: The objectives of this study were to research on the accuracy of automated hematology analyzers of various types from different manufacturers and to observe the deviation among these instruments. Fresh anticoagulated blood from healthy donors on 115 hematology analyzers in 114 different hospitals were determined. RESULTS: The maximum coefficients of variation (CVs. %) among instruments of three main manufacturers (Sysmex, Beckman Coulter and Abbott) of red blood cell count (RBC), hemoglobin (Hgb), hematocrit (Hct), white blood cell count (WBC) and platelet count (Plt) were 3.2%, 3.8%, 3.6%, 9.3% and 10.8%, respectively. The maximum deviations among these parameters of different instruments were 0.74%, 1.65%, 5.45%, 7.06% and 18.55%, respectively. By improving laboratory quality management, the results of hematology analyzer determination may be more reliable than manual methods. The difference among various manufacturers was very small about RBC, Hgb, Hct, WBC and Plt the results from all kinds of instruments will tend to be comparable.

China↗