Generation of circulating tumor cells (CTCs), a key step in tumor metastasis, occurs during surgical tumor resection, often performed under general anesthesia. Propofol is the commonly used anesthetic, but its effects on CTCs and tumor metastasis remain largely unknown. Propofol effects are investigated in an experimental metastasis model by injecting tumor cells and, subsequently, low-or standard-dose propofol to nude mice through tail vein. Propofol-or vehicle-treated tumor cells are also injected to the mice. An in vitro tumor cell-vascular endothelial cell adhesion assay, immunofluorescence, and other methods are employed to assess how propofol affects tumor cell adhesion and extension. Propofol induces more lung tumor metastasis in mice than control. Mechanistically, propofol enhances tumor cell adhesion and extension through GABA A R to downregulate TRIM21 expression, leading to upregulation of Src, a protein associated with cell adhesion. These results demonstrate that propofol may promote tumor metastasis through GABA A R-TRIM21-Src mechanism.

Acidosis, such as respiratory acidosis and metabolic acidosis, can be induced by coronavirus disease 2019 (COVID‐19) infection and is associated with increased mortality in critically ill COVID‐19 patients. It remains unclear whether acidosis further promotes SARS‐CoV‐2 infection in patients, making virus removal difficult. For antacid therapy, sodium bicarbonate poses great risks caused by sodium overload, bicarbonate side effects, and hypocalcemia. Therefore, new antacid antidote is urgently needed. Our study showed that an acidosis‐related pH of 6.8 increases SARS‐CoV‐2 receptor angiotensin‐converting enzyme 2 (ACE2) expression on the cell membrane by regulating intracellular microfilament polymerization, promoting SARS‐CoV‐2 pseudovirus infection. Based on this, we synthesized polyglutamic acid‐PEG materials, used complexation of calcium ions and carboxyl groups to form the core, and adopted biomineralization methods to form a calcium carbonate nanoparticles (CaCO3‐NPs) nanoantidote to neutralize excess hydrogen ions (H+), and restored the pH from 6.8 to approximately 7.4 (normal blood pH). CaCO3‐NPs effectively prevented the heightened SARS‐CoV‐2 infection efficiency due to pH 6.8. Our study reveals that acidosis‐related pH promotes SARS‐CoV‐2 infection, which suggests the existence of a positive feedback loop in which SARS‐CoV‐2 infection‐induced acidosis enhances SARS‐CoV‐2 infection. Therefore, antacid therapy for acidosis COVID‐19 patients is necessary. CaCO3‐NPs may become an effective antacid nanoantidote superior to sodium bicarbonate.

No abstract

AimsAnxiety disorders associated with pain are a common health problem. However, the underlying mechanisms remain poorly understood. We aimed to investigate the role of paraventricular nucleus (PVN)‐central nucleus of the amygdala (CeA) oxytocinergic projections in anxiety‐like behaviors induced by inflammatory pain.MethodsAfter inflammatory pain induction by complete Freund's adjuvant (CFA), mice underwent elevated plus maze, light–dark transition test, and marble burying test to examine the anxiety‐like behaviors. Chemogenetic, optogenetic, and fiber photometry recordings were used to modulate and record the activity of the oxytocinergic projections of the PVN‐CeA.ResultsThe key results are as follows: inflammatory pain‐induced anxiety‐like behaviors in mice accompanied by decreased activity of PVN oxytocin neurons. Chemogenetic activation of PVN oxytocin neurons prevented pain‐related anxiety‐like behaviors, whereas inhibition of PVN oxytocin neurons induced anxiety‐like behaviors in naïve mice. PVN oxytocin neurons projected directly to the CeA, and microinjection of oxytocin into the CeA blocked anxiety‐like behaviors. Inflammatory pain also decreased the activity of CeA neurons, and optogenetic activation of PVNoxytocin‐CeA circuit prevented anxiety‐like behavior in response to inflammatory pain.ConclusionThe results of our study suggest that oxytocin has anti‐anxiety effects and provide novel insights into the role of PVNoxytocin‐CeA projections in the regulation of anxiety‐like behaviors induced by inflammatory pain.