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Biomedical subjects

Kai Yang

Publications and source records attributed to Kai Yang.

4 recordsLinked to original sources

Zhiling Jiangya decoction treats hypertension in rats: An integrative study of network pharmacology, immune infiltration, molecular simulation, and 16S rDNA sequencing.

OBJECTIVE: This study integrated network pharmacology, immune infiltration analysis, molecular docking, molecular dynamics simulation, ADMET prediction, 16S rDNA sequencing, and rat experiments to elucidate the potential mechanisms underlying the antihypertensive effects of Zhiling Jiangya Decoction (ZLJYD). METHODS: Active compounds and their potential targets were screened from the PubChem, TCMSP, NovoPro, and SwissTargetPrediction databases. Hypertension-related targets were retrieved from the OMIM and GeneCards databases, and overlapping targets were identified. The STRING database and Cytoscape 3.10.1 software were used to construct a protein-protein interaction network and a herb-component-target-disease network. Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to identify the key biological processes and signaling pathways involved. Using the CIBERSORT algorithm combined with correlation analysis, we investigated the association between key targets and immune cell infiltration. Molecular docking, molecular dynamics simulations, and ADMET predictions were performed to assess the binding stability and pharmacokinetic properties of the main compounds with their corresponding targets. Finally, the antihypertensive efficacy of ZLJYD was validated using a spontaneously hypertensive rat model, and alterations in gut microbiota were analyzed using 16S rDNA sequencing. RESULTS: A total of 123 active compounds and 267 hypertension-related targets of ZLJYD were identified. Enrichment analysis revealed that these targets were primarily associated with the PI3K-Akt signaling pathway and lipid and atherosclerosis pathways. Immune infiltration analysis suggested that the therapeutic effects of ZLJYD may involve the regulation of follicular helper T cells, naïve B cells, and naïve CD4⁺ T cells. Molecular docking and dynamics simulations supported the stable binding of key compounds to their target proteins, while ADMET predictions indicated favorable pharmacokinetic properties and safety profiles. Rat experiments demonstrated that ZLJYD significantly reduced blood pressure in spontaneously hypertensive rats, partially alleviated gut microbiota dysbiosis, and altered microbial community structure and phylogenetic diversity. CONCLUSION: This study systematically elucidates the potential mechanisms underlying the antihypertensive effects of ZLJYD through multiple components, targets, and pathways, particularly immune regulation and gut microbiota remodeling. These findings provide mechanistic insights into its potential therapeutic application.

16S rDNA sequencing

Stepwise allelic trajectory of ETP2 underlies trade-off between UVB tolerance and submergence adaptation in Arabidopsis thaliana.

Strong UVB radiation critically restricts plant growth, yield, and distribution, while mechanisms enabling adaptation to intense UVB remain unclear. Here, we uncover that the F-box ubiquitin E3 ligase UVBT1 (also known as ETP2) is indispensable for UVB tolerance in A. thaliana. In the high-altitude Tibet accession, a distinctive 166-bp deletion in ETP2 promoter leads to the complete absence of the W-box element, thereby eliminating WRKY36-mediated transcriptional repression. This results in elevated ETP2 levels, which degrade EIN2 and activate the protective anthocyanin/flavonoid pathway. Conversely, in low-altitude accessions, which are often exposed to lower UVB and higher precipitation conditions, WRKY36-mediated repression of ETP2 stabilizes EIN2 and WRKY22, endowing the plants with submergence tolerance. Notably, aside from the Tibet-accession-specific 166-bp deletion, the geographical distribution of the promoter allelic shift from C to G near the ETP2 W-box within the 166-bp region is tightly associated with UVB radiation with increasing altitudes for the other global accessions. This allelic change also enhances WRKY36-mediated repression of ETP2, suggesting an additional stepwise adaptation process. This work thus defines the WRKY36-ETP2-EIN2/WRKY22 module as a key regulator of UVB tolerance and submergence adaptation, potentially enabling A. thaliana to adapt to environments with varying UVB and precipitation conditions.

Arabidopsis

POFUT1 Serves as an Independent Prognostic Factor and Therapeutic Target by Activating the PI3K/AKT Pathway in Glioma.

OBJECTIVE: Protein O-fucosyltransferase 1 (POFUT1) has been implicated in several malignancies, but its functional and prognostic significance in glioma remains insufficiently defined. This study evaluated whether POFUT1 expression is associated with glioma progression, patient outcome, and PI3K/AKT pathway activity. METHODS: Public glioma transcriptome datasets from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) were analyzed and compared with clinical samples collected from 123 glioma patients. POFUT1 protein levels in clinical specimens were determined by immunohistochemical staining, and its association with patient outcome was analyzed using survival curves. In vitro, glioma cell growth, motility, and invasiveness were examined using MTT and Transwell assays. The effect of POFUT1 on tumor formation was further tested in a subcutaneous xenograft model. RNA sequencing, KEGG pathway enrichment, and pharmacological inhibition were then used to explore the mechanism linking POFUT1 to PI3K/AKT signaling. RESULTS: POFUT1 expression was higher in glioma than in normal brain tissue and increased with tumor grade. Patients with high POFUT1 levels had shorter overall survival, and multivariate Cox analyses supported POFUT1 as an independent prognostic indicator. Incorporating POFUT1 into a nomogram improved prediction of 1-, 3-, and 5-year survival. Functionally, POFUT1 knockdown reduced glioma cell growth, motility, invasion, and xenograft expansion, whereas POFUT1 overexpression produced the opposite phenotype. Transcriptomic and protein analyses indicated that POFUT1 enhanced PI3K/AKT signaling. The PI3K inhibitor LY294002 weakened the tumor-promoting effects caused by POFUT1 overexpression. CONCLUSION: POFUT1 as a key driver of glioma malignancy, predominantly through activating the PI3K-AKT signaling pathway. These findings highlight POFUT1 as a promising novel therapeutic target for aggressive glioma.

Glioma

Transcriptome analysis of the diseased intervertebral disc tissue in patients with spinal tuberculosis.

OBJECTIVE: To investigate the differential expression genes (DEGs) in spinal tuberculosis using transcriptomics, with the aim of identifying novel therapeutic targets and prognostic indicators for the clinical management of spinal tuberculosis. METHODS: Patients who visited the Department of Orthopedics at the Second Hospital, Lanzhou University from January 2021 to May 2023 were enrolled. Based on the inclusion and exclusion criteria, there were 5 patients in the test group and 5 patients in the control group. Total RNA was extracted and paired-end sequencing was conducted on the sequencing platform. After processing the sequencing data with clean reads and annotating the reference genome, FPKM normalization and differential expression analysis were performed. The DEGs and long non-coding RNAs (LncRNAs) were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. The cis-regulation of differentially expressed mRNAs (DE mRNAs) by LncRNAs was predicted and analyzed to establish a co-expression network. RESULTS: This study identified 2366 DEGs, with 974 genes significantly upregulated and 1392 genes significantly downregulated. The upregulated genes are associated with cytokine-cytokine receptor interactions, tuberculosis, and TNF-α signaling pathways, primarily enriched in biological processes such as immunity and inflammation. The downregulated genes are related to muscle development, contraction, fungal defense response, and collagen metabolism processes. Analysis of LncRNAs from bone tuberculosis RNA-seq data detected a total of 3652 LncRNAs, with 356 significantly upregulated and 184 significantly downregulated. Further analysis identified 311 significantly different LncRNAs that could cis-regulate 777 target genes, enriched in pathways such as muscle contraction, inflammatory response, and immune response, closely related to bone tuberculosis. There are 51 genes enriched in the immune response pathway regulated by cis-acting LncRNAs. LncRNAs that regulate immune response-related genes, such as upregulated RP11-451G4.2, RP11-701P16.5, AC079767.4, AC017002.1, LINC01094, CTA-384D8.35, and AC092484.1, as well as downregulated RP11-2C24.7, may serve as potential prognostic and therapeutic targets. CONCLUSION: The DE mRNAs and LncRNAs in spinal tuberculosis are both associated with immune regulatory pathways. These pathways promote or inhibit the tuberculosis infection and development at the mechanistic level and play an important role in the process of tuberculosis transferring to bone tissue.

Humans