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Objective: To study the expressions and activities of Rho GTPases in hypoxia and its relationship with tumor angiogenesis.
Methods: Three tumor cell lines were used in this study: gastric cancer cell lines AGS, SGC7901 and hepatocellular carcinoma cell line HepG2. Expression level of Rac1 mRNA was detected by semi-quantitative RT-PCR. Activity of Rac1 was determined by pull-down assay and expression of HIF-1alpha, VEGF, p53 and PTEN protein was detected by Westernblot.
Results: The expression level of Rac1 mRNA was significantly increased in hypoxia compared to normoxia. Pull-down assay showed that hypoxia-induced activity of Rac1 was elevated in a time-dependent manner and climaxed at 3 hours. The expressions of HIF-1alpha and VEGF protein were up-regulated, while those of PTEN and p53 protein were down-regulated.
Conclusion: These results indicate that hypoxia enhances Rac1 expression which might be involved in tumor angiogenesis by reacting with hypoxia-responsive genes.
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Mol Inform
September 2025
Department of Computational Chemistry, "Coriolan Drăgulescu" Institute of Chemistry Timișoara, Romanian Academy, Timișoara, Romania.
Docking is a structure-based cheminformatics tool broadly employed in early drug discovery. Based on the tridimensional structure of the protein target, docking is used to predict the binding interactions between the protein and a ligand, estimate the corresponding binding affinity, or perform virtual screenings (VSs) to identify new active compounds. This study introduces the ligand B-factor index (LBI), a novel computational metric for prioritizing protein-ligand complexes for docking.
View Article and Find Full Text PDFBioessays
September 2025
MY Small G Protein Research Group, Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Pulau Pinang, Malaysia.
Advanced biosensing technologies, such as Förster resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET), have enabled real-time, high-resolution tracking of Rho GTPase activity, surpassing traditional methods like pull-down assays. However, current biosensors mainly detect the GTP-bound active state through effector interactions, without directly measuring Rho GTPase expression or identifying related biomarkers of abnormal activation. Small Rho GTPases are essential molecular switches that regulate key cellular processes such as cytoskeletal organization, cell movement, polarity, vesicle trafficking, and the cell cycle.
View Article and Find Full Text PDFPLoS One
September 2025
Institute of Computational Science and Technology, Guangzhou University, Guangzhou, China.
MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology, yet their spatial dynamics within tumor microenvironments (TMEs) remain underexplored due to technical limitations in current spatial transcriptomics (ST) technologies. To address this gap, we present STmiR, a novel XGBoost-based framework for spatially resolved miRNA activity prediction. STmiR integrates bulk RNA-seq data (TCGA and CCLE) with spatial transcriptomics profiles to model nonlinear miRNA-mRNA interactions, achieving high predictive accuracy (Spearman's ρ > 0.
View Article and Find Full Text PDFCardiol Rev
September 2025
Departments of Medicine and Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY.
Heart failure (HF) is a complex clinical syndrome marked by impaired contractility, adverse remodeling, and dysregulated intracellular signaling. Protein kinases are central regulators of cardiac function, modulating calcium handling, gene transcription, hypertrophy, and apoptosis through phosphorylation of target proteins. In HF, chronic activation of kinases such as protein kinase A, protein kinase C, calcium/calmodulin-dependent kinase II, mitogen-activated protein kinases, protein kinase B, and Rho-associated protein kinase contributes to progressive cardiac dysfunction.
View Article and Find Full Text PDFAllergol Immunopathol (Madr)
September 2025
Department of Respiratory and Critical Care Medicine, the Wenzhou Central Hospital and Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Background: Acute lung injury (ALI) is a critical clinical condition with high mortality, necessitating the development of more effective therapeutic strategies. Rho Guanine nucleotide dissociation inhibitor (GDP) beta (ARHGDIB) has been shown to exert protective effects against noxious stimuli in various disease models.
Objective: In this study, we investigated whether ARHGDIB knockdown had a protective effect on lipopolysaccharide (LPS)-induced injury in alveolar epithelial cells and elucidated its underlying molecular mechanisms.