Targeting ZDHHC9 potentiates anti-programmed death-ligand 1 immunotherapy of pancreatic cancer by modifying the tumor microenvironment.

Immune checkpoint blockade (ICB) therapy targeting the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) axis has achieved considerable success in treating a wide range of cancers. However, most patients with pancreatic cancer remain resistant to ICB. Moreover, there is a lack of optimal biomarkers for the prediction of response to this therapy.

Choroid plexus-selective inactivation of adenosine A receptors protects against T cell infiltration and experimental autoimmune encephalomyelitis.

Background: Multiple sclerosis (MS) is one of the most common autoimmune disorders characterized by the infiltration of immune cells into the brain and demyelination. The unwanted immunosuppressive side effect of therapeutically successful natalizumab led us to focus on the choroid plexus (CP), a key site for the first wave of immune cell infiltration in experimental autoimmune encephalomyelitis (EAE), for the control of immune cells trafficking. Adenosine A receptor (AR) is emerging as a potential pharmacological target to control EAE pathogenesis.

Accumbal Adenosine A Receptors Enhance Cognitive Flexibility by Facilitating Strategy Shifting.

The deficits of cognitive flexibility (including attentional set-shifting and reversal learning) concomitant with dysfunction of the striatum are observed in several neuropsychiatric disorders. Rodent and human studies have identified the striatum [particularly the dorsomedial striatum (DMS) and nucleus accumbens (NAc)] as the critical locus for control of cognitive flexibility, but the effective neuromodulator and pharmacological control of cognitive flexibility remains to be determined. The adenosine A receptors (ARs) are highly enriched in the striatopallidal neurons where they integrate dopamine and glutamate signals to modulate several cognitive behaviors, but their contribution to cognitive flexibility control is unclear.

Spatiotemporal Control of GPR37 Signaling and Its Behavioral Effects by Optogenetics.

Despite the progress in deorphanization of G Protein-Coupled Receptors (GPCRs), ≈100 GPCRs are still classified as orphan receptors without identified endogenous ligands and with unknown physiological functions. The lack of endogenous ligands triggering GPCR signaling has hampered the study of orphan GPCR functions. Using GPR37 as an example, we provide here the first demonstration of the channelrhodopsin 2 (ChR2)-GPCR approach to bypass the endogenous ligand and selectively activate the orphan GPCR signal by optogenetics.

Neonatal inflammation induces reorganization in dendritic morphology of retinal ganglion cells but not their retinogeniculate projection in mice.

Perinatal inflammatory insult in preterm babies is associated with vision impairment, but the underlying cellular mechanism is still unknown. In this study, we set out to explore whether systemic inflammatory stress affects the development of retinal ganglion cells (RGCs). Neonatal inflammation was induced by single and systemic injection of lipopolysaccharide (LPS, 1 mg/kg) at postnatal day 4 (P4).