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Background: Muscarinic receptor agonism and positive allosteric modulation is a promising mechanism of action for treating psychosis, not present in most D2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis to provide unique insights and evidence-based information to guide drug development.

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Objective: This study aims to explore the therapeutic mechanism of Massa Medicata Fermentata (MMF) with different formulations on spleen deficiency constipation in mice by analyzing gastrointestinal hormones, D-xylose, intestinal microbiota, and intestinal enzyme activities.

Methods: A spleen deficiency constipation model was established using an oral administration of Sennae Folium decoction combined with controlled diet and water intake. After successful model establishment, the mice with spleen deficiency constipation were treated with MMF S1, S2, S3.

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This study investigated the mechanisms employed by exogenous dopamine application in alleviating chilling injury in kiwifruits during storage at 1 °C for 120 days. Our results indicated that dopamine treatment at 150 µM alleviated chilling injury in kiwifruits during storage at 1 °C for 120 days. By 150 µM dopamine application, higher SUMO E3 ligase (SIZ1) and target of rapamycin (TOR) genes expression accompanied by lower poly(ADP-Ribose) polymerase 1 (PARP1) and sucrose non-fermenting 1-related kinase 1 (SnRK1) genes expression was associated with higher salicylic acid, ATP, NADPH and proline accumulation in kiwifruits during storage at 1 °C for 120 days.

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Microglia and the border-associated macrophages contribute to the modulation of cerebral blood flow, but the mechanisms have remained uncertain. Here, we show that microglia regulate the cerebral blood flow baseline and the responses to whisker stimulation or intra-cisternal magna injection of adenosine triphosphate, but not intra-cisternal magna injection of adenosine in mice model. Notably, microglia repopulation corrects these cerebral blood flow anomalies.

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Neuronal processing of external sensory input is shaped by internally generated top-down information. In the neocortex, top-down projections primarily target layer 1, which contains NDNF (neuron-derived neurotrophic factor)-expressing interneurons and the dendrites of pyramidal cells. Here, we investigate the hypothesis that NDNF interneurons shape cortical computations in an unconventional, layer-specific way, by exerting presynaptic inhibition on synapses in layer 1 while leaving synapses in deeper layers unaffected.

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