Ganoderic acid T, a Ganoderma triterpenoid, modulates the tumor microenvironment and enhances the chemotherapy and immunotherapy efficacy through downregulating galectin-1 levels.

Ganoderic acid T (GAT), a triterpenoid molecule of Ganoderma lucidum, exhibits anti-cancer activity; however, the underlying mechanisms remain unclear. Therefore, in this study, we aimed to investigate the anti-cancer molecular mechanisms of GAT and explore its therapeutic applications for cancer treatment. GAT exhibited potent anti-cancer activity in an ES-2 orthotopic ovarian cancer model in a humanized mouse model, leading to significant alterations in the tumor microenvironment (TME).

NMDA receptors sustain but do not initiate neuronal depolarization in spreading depolarization.

Spreading depolarization (SD) represents a neurological process characterized by a massive, self-sustaining wave of brain cell depolarization. Understanding its mechanism is important for treating ischemic or hemorrhagic stroke and migraine with aura. Many believed that ion fluxes through NMDA receptors (NMDARs) are responsible for neuronal transmembrane currents of SD.

Spreading Depression Promotes Astrocytic Calcium Oscillations and Enhances Gliotransmission to Hippocampal Neurons.

Spreading depression (SD) is a pathophysiological phenomenon characterized by propagating waves of profound neuronal and glial depolarization in central nervous system gray matter. Although SD is primarily mediated by neurons with a subsequent astrocytic response, it remains unclear how astrocytic activity is modulated after SD and how altered astrocyte signaling contribute to neuronal excitability. Here, we report that after the concurrent Ca2+ wave, SD enhanced astrocytic activity by promoting a secondary period of Ca2+ oscillations.

Effects of anti-epileptic drugs on spreading depolarization-induced epileptiform activity in mouse hippocampal slices.

Epilepsy and spreading depolarization (SD) are both episodic brain disorders and often exist together in the same individual. In CA1 pyramidal neurons of mouse hippocampal slices, induction of SD evoked epileptiform activities, including the ictal-like bursts, which occurred during the repolarizing phase of SD, and the subsequent generation of paroxysmal depolarization shifts (PDSs), which are characterized by mild depolarization plateau with overriding spikes. The duration of the ictal-like activity was correlated with both the recovery time and the depolarization potential of SD, whereas the parameters of PDSs were not significantly correlated with the parameters of SD.