Biomedical subjects

Xiang Lv

Publications and source records attributed to Xiang Lv.

5 recordsLinked to original sources

PubMed2026

Multi-omics identification of therapeutic targets of compound sappan decoction in hepatocellular carcinoma.

BACKGROUND: Compound sappan decoction (CSD) is a multi-herbal traditional Chinese medicine formulation with clinical relevance in hepatocellular carcinoma (HCC). However, its therapeutic mechanisms remain unclear. METHODS: Bioactive compounds of CSD were identified and standardized using pharmacological and chemical databases. Potential targets were predicted via multiple target inference platforms. HCC-related genes were curated from comprehensive disease databases. Summary-data-based Mendelian randomization (SMR) was conducted to infer causal relationships between compound targets and HCC risk using large-scale quantitative trait loci (QTL) datasets and HCC genome-wide association study data. Colocalization analysis, protein-protein interaction (PPI) network construction, and GO/KEGG enrichment were performed on SMR-identified targets. Molecular docking evaluated binding affinities of representative compounds to prioritized targets. RESULTS: A total of 784 overlapping genes between predicted CSD targets and HCC-related genes were subjected to SMR analysis. Among these, 22 targets were significantly associated with HCC risk based on transcriptomic or proteomic QTLs and showed colocalization evidence. Notably, four targets (ADRB2, APOE, SYK, and PGF) were supported by both replication in an independent cohort and strong colocalization. These 22 targets were enriched in apoptosis, PI3K-Akt signaling, redox metabolism, and detoxification pathways. PPI analysis revealed central hubs including MMP9, BCL2, CASP1, and MCL1. Molecular docking demonstrated strong binding of APOE to quercetin, PGF to luteolin-7-olate, and SYK to kaempferol. CONCLUSIONS: CSD may exert therapeutic effects on HCC through modulation of genetically validated targets involved in tumor progression, inflammation, and metabolic reprogramming, supporting its potential clinical utility as an adjunctive treatment strategy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12672-026-04740-8.

Caesalpinia↗

PubMed2005

A conserved, extended chromatin opening within alpha-globin locus during development.

Histone modifications play an important role in eukaryotic gene regulation. However, the dynamic alteration of histone modification during development is poorly understood. In addition, the relationship between histone modification and globin gene switching remains unclear. Here, we assessed the dynamic pattern of histone modification (H3 acetylation, H4 acetylation, H3 K4 methylation, and H3 K79 methylation) along the murine alpha-globin locus, as well as along the human alpha-globin locus in transgenic mice, during globin gene switching in vivo. During the switching, histone modification at embryonic zeta-gene and fetal/adult alpha-genes displayed different developmental patterns. The level of histone modification at zeta-gene was developmentally regulated, in accordance with the level of zeta-gene expression, whereas the alpha-genes kept high level of histone modification at both developmental stages, regardless of their expression levels. Histone deacetylase inhibition selectively increased acetylation at the inactive zeta-gene in fetal livers, although it did not reactivate the gene expression. More importantly, an obvious increasing of histone modification level at major regulatory elements and fetal/adult alpha-genes was observed during the switching, suggesting that a conserved, extended chromatin opening within the locus occurs during globin gene switching.

Acetylation↗

PubMed2005

High fidelity screening of regulatory sequences in apolipoprotein(a)-plasminogen cluster.

Identifying networks of gene expression regulation is one of the major tasks in the post-genomic era, this demands firstly high throughput identification of regulatory elements. Apolipoprotein(a)-plasminogen cluster is closely related to both atherosclerosis and thrombosis, and forms a link between the two systems. The mechanism regulating expression of this cluster, through which the balance between atherosclerosis and thrombosis is achieved, is far from been fully understood. Polymerase chain reaction based strategies for screening of regulatory sequences are both simple and efficient yet face severe problems of contamination and sequence mutations. In this work, entity self-competition electrophoresis mobility shift assay and differential library hybridization are introduced to overcome the problems. Cis-element candidates are picked out from a library generated from the screening region, thus avoiding the effect of repetitive amplifications. Sequence fidelity of the selected fragments is guaranteed and one by one identification of each fragment by self-competition is unnecessary. Using this method, 32 potential regulatory elements in apolipoprotein(a)-plasminogen gene cluster were found, including three of the four known DNase I hypersensitive sites in the cluster, attesting the efficiency of our method. We also find an intron-locating element, which is repeatedly screened out. A new in vivo electrophoresis mobility shift assay method based on in situ digestion of crosslinked chromatin DNA and southern hybridization is established for the detection of in vivo protein binding status in the intron region. The result supports our hypothesis that the element may play an important role in expression regulation or evolution of apolipoprotein(a) gene.

Apolipoprotein A-I↗

PubMed2002

Screening regulatory sequences from bacterial artificial chromosome DNA of alpha- and beta-globin gene clusters.

In the forthcoming postgenomic era, identification of regulatory DNA sequences is becoming increasingly important for characterizing DNA-binding proteins and for elucidating the regulatory mechanisms of gene expression. Presently, there lack efficient methods to broadly screen and identify DNA regulatory elements on a large scale. We established herein an efficient strategy to screen regulatory sequences from bacterial artificial chromosome (BAC) DNAs containing human alpha- and beta-globin gene clusters based on polymerase chain reaction and electrophoretic mobility shift assay (EMSA) techniques without purified transcription factors. Twenty-three subclones derived from alpha-BAC DNA by bulk EMSA selection retained the ability to bind nuclear proteins of K562 cells when retested by EMSA. In 19 clones sequenced, 14 are identical to those registered in GenBank and five have one base difference. All of the 24 randomly picked beta-BAC clones showed specific binding with nuclear proteins of K562 cells. In 11 clones sequenced, eight are identical to those registered in GenBank and three have one base difference. This approach could be particularly powerful if combined with other systematic methods for identifying cis-regulatory DNA elements.

Binding Sites↗

PubMed2002

High-mobility group protein 2 may be involved in the locus control region regulation of the beta-globin gene cluster.

Expression regulation of the beta-globin gene cluster is a result of synergistic interactions between cis-elements and trans-acting factors. Previous studies usually concentrated on the core sequence of each hypersensitive site in the locus control region of the beta-globin gene cluster. But more and more evidence illustrates that the flanking regions are indispensable also. Using electrophoretic mobility shift assay and solid-phase DNase I footprinting methods, we identified a small nuclear protein from K562 cells that binds specifically to the first AT-rich region flanking the hypersensitive site 2 core sequence of the human beta-globin gene locus control region. N-terminal sequencing of the enriched protein proved that it is a member of the high-mobility group protein 2 family. This indicates that the AT-rich region in human hypersensitive site 2 may take part in the regulation of the beta-globin gene cluster by facilitating DNA bending, which is a prerequisite for the looping mechanism in this region.

Base Sequence↗