Post-stroke neurological deficits and mortality are often associated with vascular disruption and neuronal apoptosis. Galectin-3 (Gal3) is a potent pro-survival and angiogenic factor. However, little is known about its protective role in the cerebral ischemia/reperfusion (I/R) injury. We have previously shown significant up-regulation of Gal3 in the post-stroke rat brain, and that blocking of Gal3 with neutralizing antibody decreases the cerebral blood vessel density. Our current study demonstrates that intracerebral local delivery of the Gal3 into rat brain at the time of reperfusion exerts neuroprotection. Ischemic lesion volume and neuronal cell death were significantly reduced as compared with the vehicle-treated MCAO rat brains. Gal3 increased vessel density and neuronal survival after I/R in rat brains. Importantly, Gal3-treated groups showed significant improvement in motor and sensory functional recovery. Gal3 increased neuronal cell viability under in vitro oxygen–glucose deprivation conditions in association with increased phosphorylated-Akt, decreased phosphorylated-ERK1/2, and reduced caspase-3 activity. Gene expression analysis showed down regulation of pro-apoptotic and inflammatory genes including Fas-ligand, and upregulation of pro-survival and pro-angiogenic genes including Bcl-2, PECAM, and occludin. These results indicate a key role for Gal3 in neuro-vascular protection and functional recovery following ischemic stroke through modulation of angiogenic and apoptotic pathways.

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showed that some retained their ENZA resistance while others regained ENZA-sensitivity. Transcriptomic analyses revealed significant upregulation of WNT5A, EMT and neuronal programs. Single cell analyses revealed heterogeneous sub-populations that behaved as cancer stem cells in 3D/organoid cultures.CONCLUSIONS: Our patient derived xenograft models demonstrate that the bone niche promotes tumor growth even when treated with anti-androgen. Tumor growth is inhibited when injected subcutaneously, resembling the effectiveness of androgen deprivation therapy toward localized prostate cancer. This elucidates the importance of utilizing in vivo patient derived models to gain a better understanding of why the bone niche supports tumor growth.

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