CDH5 (Cadherin 5)

Targeting the VEGFR2/PLCγ/SHP2 axis-genetically or pharmacologically-reduces EC junctional phosphorylation to prevent VE-cadherin internalization, followed by reduced macromolecular leakage. Tumor EC expression of PLCγ or SHP2 is associated with vascular leakage in human kidney cancer, underscoring their potential as targets for vascular normalization and biomarkers for disease progression and treatment response.

Chemoproteomic and biophysical analyses reveal that erianin targets P4HA1 at the Arg379 site within the α-ketoglutarate (α-KG) binding pocket, leading to downregulation of the HIF1α/SNAIL/SLUG pathway, thereby restoring endothelial integrity by stabilizing VE-cadherin-mediated junctions and upregulating ICAM1 to enhance T-cell adhesion. These findings highlight erianin's potential to overcome vascular barriers and reprogram the tumor microenvironment, providing a novel therapeutic strategy to enhance immunotherapy in GBM and other solid tumors.

FKBPL-based peptide mimetic, AD-01 (1 nM), in high-glucose conditions, upregulated endothelial vcam1 and glut1 mRNA expression, independent of miR-302b-5p. FKBPL plays an important role in glucose metabolism, endothelial function, angiogenesis, cardiac inflammation and function, and could be explored as a therapeutic target of cardiovascular disease both in nondiabetes and diabetes settings using precision medicine approach.

Here, using a bleomycin-induced experimental lung fibrosis model, we observed that RAP2A expression was markedly upregulated in pulmonary endothelial cells and correlated with disease severity...In vitro assays further demonstrated that RAP2A deficiency impaired tumor necrosis factor-α-induced endothelial adhesiveness without affecting basal endothelial integrity. Collectively, our findings identify endothelial RAP2A as a regulator of inflammatory endothelial activation in experimental lung fibrosis and suggest that targeting RAP2A-mediated signaling may represent a potential strategy to modulate endothelial-immune crosstalk during fibrotic lung injury.

This controlled vascular remodeling established a pronounced size-dependent permeability window, defined by locally induced gap dimensions that varied across tumor types, permitting efficient penetration of nanoparticles ≤200 nm while largely excluding particles >500 nm. By uniting nanotechnology, vascular biology, and artificial intelligence, this interdisciplinary framework provides a mechanistic and predictive paradigm for overcoming vascular barriers and advancing the rational design of tumor-targeted nanomedicines.

DOKs confined to the top channel showed slight and uneven E-cadherin and EpCAM (Epithelial Cell Adhesion Molecule) positivity, but evident positivity for Trop-2, confirming that their phenotype differed from that of healthy epithelial cells. The presented OD-OoC could enable in vitro monitoring of epithelial cell phenotype changes and cell migration across the membrane, suggesting its potential applicability in future oral cancer research.

The findings indicate a time-dependent regulation of Fn14 under ischemic conditions in vitro, highlighting its role in BBB stress and recovery. Nevertheless, further preclinical studies are needed to establish its therapeutic potential.

TIPE2 knockout attenuates hemorrhagic shock-induced acute lung injury through mechanisms involving downregulation of inflammatory-associated protein expression, suppression of proinflammatory cytokine release, and restoration of pulmonary barrier permeability.

While conditioned media from SLPI-overexpressing cells did not affect angiogenesis, these cells promoted vasculogenic mimicry, with increased expression of VEGFA and VE-cadherin, and decreased N-cadherin. These findings suggest that SLPI promotes cholangiocarcinoma progression through inflammation-associated and vasculogenic mechanisms, highlighting its potential as a candidate molecular target for therapeutic intervention.

Cellular experiments demonstrated that TMEM59L overexpression enhanced proliferation, migration, invasion, and induced EMT (decreased E-cadherin; increased N-cadherin, VE-cadherin, and MMP14) in HCT116 cells. TMEM59L shows promise as a diagnostic and prognostic biomarker in COAD, with potential roles in modulating the TME, EMT, and immunotherapy response.

This study delineates the profound impact of nucleotide metabolic reprogramming on epithelial cell states, immune ecology, and malignant evolution in LUAD. The NMRS provides a robust predictor of prognosis and immunotherapy response across cohorts, while ENO1 emerges as a pivotal metabolic-immune mediator and promising therapeutic target.

At present, targeted therapies do not account for this variability; generally, responses are not based on pathology. Spatial changes in the tumor microenvironment that may provide insights into drug action and resistance mechanisms are missed.