The Histone Lysine Demethylase KDM7A Contributes to Reward Memory via Fscn1-Induced Synaptic Plasticity in the Medial Prefrontal Cortex.

Lysine demethylase 7A (KDM7A) catalyzes the removal of dimethylation from histone H3 lysine 9 and lysine 27, both of which are associated with transcription repression. Previous study indicates that Kdm7a mRNA in the medial prefrontal cortex (mPFC) increases after drug exposure, yet its role in drug-related behaviors is largely unknown. In a morphine-conditioned place preference (CPP) paradigm, these findings reveal a specific increase of Kdm7a expression in the mPFC 7 days after drug withdrawal.

The 5-HT receptors in the VLO contribute to the development of morphine-induced behavioral sensitization in rats.

The 5-hydroxytryptamine 7 receptor (5-HTR) is one of the most recently cloned serotonin receptors which have been implicated in many physiological and pathological processes including drug addiction. Behavioral sensitization is the progressive process during which re-exposure to drugs intensified the behavioral and neurochemical responses to drugs. Our previous study has demonstrated that the ventrolateral orbital cortex (VLO) is critical for morphine-induced reinforcing effect.

Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway.

Traumatic brain injury (TBI) is a universal leading cause of long-term neurological disability and causes a huge burden to an ever-growing population. Moderate intensity of treadmill exercise has been recognized as an efficient intervention to combat TBI-induced motor and cognitive disorders, yet the underlying mechanism is still unclear. Ferroptosis is known to be highly implicated in TBI pathophysiology, and the anti-ferroptosis effects of treadmill exercise have been reported in other neurological diseases except for TBI.

Synthesis of 3'-O-Alkyl Homologues and a Biotin Probe of Isorhamnetin and Evaluation of Cytotoxic Efficacy on Cancer Cells.

Isorhamnetin is a natural flavonoid which shows a variety of biological activities such as antioxidant, anti-inflammatory and antitumor. In order to identify the cellular binding protein of isorhamnetin as potential anti-cancer target, we first synthesized 3'-O-substituted quercetin as isorhamnetin homologues and evaluated the growth inhibitory activity of these derivatives on breast, colon and prostate cancer cell lines. The preliminary results showed that the 3'-O modification did not affect the cytotoxic activity of the scaffold.

Dynamic Changes of Cytoskeleton-Related Proteins Within Reward-Related Brain Regions in Morphine-Associated Memory.

Drug-induced memory engages complex and dynamic processes and is coordinated at multiple reward-related brain regions. The spatiotemporal molecular mechanisms underlying different addiction phases remain unknown. We investigated the role of β-actin, as well as its potential modulatory protein activity-regulated cytoskeletal-associated protein (Arc/Arg3.

Optical Control of the GTP Affinity of K-Ras(G12C) by a Photoswitchable Inhibitor.

Photocontrol of protein activity is an emerging field in biomedicine. For optical control of a mutant small GTPase K-Ras(G12C), we developed small-molecule inhibitors with photoswitchable efficacy, where one configuration binds the target protein and exert different pharmacological effects upon light irradiation. The compound design was based on the structure feature of a previously identified allosteric pocket of K-Ras(G12C) and the chemical structure of covalent inhibitors, and resulted in the synthesis and characterization of two representative azobenzene-containing compounds.