20 research outputs found
Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms
Intracellular gap (iGap) formation in liver sinusoidal endothelial cells (LSECs) is caused by the destruction of fenestrae and appears under pathological conditions; nevertheless, their role in metastasis of cancer cells to the liver remained unexplored. We elucidated that hepatotoxin-damaged and fibrotic livers gave rise to LSECs-iGap formation, which was positively correlated with increased numbers of metastatic liver foci after intrasplenic injection of Hepa1-6 cells. Hepa1-6 cells induced interleukin-23-dependent tumor necrosis factor-α (TNF-α) secretion by LSECs and triggered LSECs-iGap formation, toward which their processes protruded to transmigrate into the liver parenchyma. TNF-α triggered depolymerization of F-actin and induced matrix metalloproteinase 9 (MMP9), intracellular adhesion molecule 1, and CXCL expression in LSECs. Blocking MMP9 activity by doxycycline or an MMP2/9 inhibitor eliminated LSECs-iGap formation and attenuated liver metastasis of Hepa1-6 cells. Overall, this study revealed that cancer cells induced LSEC-iGap formation via proinflammatory paracrine mechanisms and proposed MMP9 as a favorable target for blocking cancer cell metastasis to the liver
Leaching Behavior of Harmful Components from Cement Solidities of Fluidized-Bed Coal Ash
Reduction of Adverse Effects by a Mushroom Product, Active Hexose Correlated Compound (AHCC) in Patients With Advanced Cancer During Chemotherapy—The Significance of the Levels of HHV-6 DNA in Saliva as a Surrogate Biomarker During Chemotherapy
AzoCholine Enables Optical Control of Alpha 7 Nicotinic Acetylcholine Receptors in Neural Networks
Nicotinic
acetylcholine receptors (nAChRs) are essential for cellular
communication in higher organisms. Even though a vast pharmacological
toolset to study cholinergic systems has been developed, control of
endogenous neuronal nAChRs with high spatiotemporal precision has
been lacking. To address this issue, we have generated photoswitchable
nAChR agonists and re-evaluated the known photochromic ligand, BisQ.
Using electrophysiology, we found that one of our new compounds, AzoCholine,
is an excellent photoswitchable agonist for neuronal α7 nAChRs,
whereas BisQ was confirmed to be an agonist for the muscle-type nAChR.
AzoCholine could be used to modulate cholinergic activity in a brain
slice and in dorsal root ganglion neurons. In addition, we demonstrate
light-dependent perturbation of behavior in the nematode, Caenorhabditis elegans
AzoCholine Enables Optical Control of Alpha 7 Nicotinic Acetylcholine Receptors in Neural Networks
Nicotinic
acetylcholine receptors (nAChRs) are essential for cellular
communication in higher organisms. Even though a vast pharmacological
toolset to study cholinergic systems has been developed, control of
endogenous neuronal nAChRs with high spatiotemporal precision has
been lacking. To address this issue, we have generated photoswitchable
nAChR agonists and re-evaluated the known photochromic ligand, BisQ.
Using electrophysiology, we found that one of our new compounds, AzoCholine,
is an excellent photoswitchable agonist for neuronal α7 nAChRs,
whereas BisQ was confirmed to be an agonist for the muscle-type nAChR.
AzoCholine could be used to modulate cholinergic activity in a brain
slice and in dorsal root ganglion neurons. In addition, we demonstrate
light-dependent perturbation of behavior in the nematode, Caenorhabditis elegans
AzoCholine Enables Optical Control of Alpha 7 Nicotinic Acetylcholine Receptors in Neural Networks
Nicotinic
acetylcholine receptors (nAChRs) are essential for cellular
communication in higher organisms. Even though a vast pharmacological
toolset to study cholinergic systems has been developed, control of
endogenous neuronal nAChRs with high spatiotemporal precision has
been lacking. To address this issue, we have generated photoswitchable
nAChR agonists and re-evaluated the known photochromic ligand, BisQ.
Using electrophysiology, we found that one of our new compounds, AzoCholine,
is an excellent photoswitchable agonist for neuronal α7 nAChRs,
whereas BisQ was confirmed to be an agonist for the muscle-type nAChR.
AzoCholine could be used to modulate cholinergic activity in a brain
slice and in dorsal root ganglion neurons. In addition, we demonstrate
light-dependent perturbation of behavior in the nematode, Caenorhabditis elegans