GNAS mutations suppress cell invasion by activating MEG3 in growth hormone–secreting pituitary adenoma

Approximately 30%–40%of growth hormone–secreting pituitary adenomas(GHPAs)harbor somatic activating mutations in GNAS(αsubunit of stimulatory G protein).Mutations in GNAS are associated with clinical features of smaller and less invasive tumors.However,the role of GNAS mutations in the invasiveness of GHPAs is unclear.GNAS mutations were detected in GHPAs using a standard polymerase chain reaction(PCR)sequencing procedure.The expression of mutation-associated maternally expressed gene 3(MEG3)was evaluated with RT-qPCR.MEG3 was manipulated in GH3 cells using a lentiviral expression system.Cell invasion ability was measured using a Transwell assay,and epithelial–mesenchymal transition(EMT)-associated proteins were quantified by immunofluorescence and western blotting.Finally,a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness.The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS.Consistently,the invasiveness of mutant GNASexpressing GH3 cells decreased.MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS.Accordingly,MEG3 upregulation inhibited tumor cell invasion,and conversely,MEG3 downregulation increased tumor cell invasion.Mechanistically,GNAS mutations inhibit EMT in GHPAs.MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway,which was further validated in vivo.Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/β-catenin signaling pathway.

Predictors and dynamic online nomogram for postoperative delayed hyponatremia after endoscopic transsphenoidal surgery for pituitary adenomas:a single-center,retrospective,observational cohort study with external validation

Background Postoperative delayed hyponatremia(PDH)is a major cause of readmission after endoscopic transsphenoidal surgery(eTSS)for pituitary adenomas(PAs).However,the risk factors associated with PDH have not been well established,and the development of a dynamic online nomogram for predicting PDH is yet to be realized.We aimed to investigate the predictive factors for PDH and construct a dynamic online nomogram to aid in its prediction.Methods We analyzed the data of 226 consecutive patients who underwent eTSS for PAs at the Department of Neurosurgery in Jinling Hospital between January 2018 and October 2020.An additional 97 external patients were included for external validation.PDH was defined as a serum sodium level below 137 mmol/L,occurring on the third postoperative day(POD)or later.Results Hyponatremia on POD 1-2(OR=2.64,P=0.033),prothrombin time(PT)(OR=1.78,P=0.008),and percentage of monocytes(OR=1.22,P=0.047)were identified as predictive factors for PDH via multivariable logistic regression analysis.Based on these predictors,a nomogram was constructed with great discrimination in internal validation(adjusted AUC:0.613-0.688)and external validation(AUC:0.594-0.617).Furthermore,the nomogram demonstrated good performance in calibration plot,Brier Score,and decision curve analysis.Subgroup analysis revealed robust predictive performance in patients with various clinical subtypes and mild to moderate PDH.Conclusions Preoperative PT and the percentage of monocytes were,for the first time,identified as predictive factors for PDH.The dynamic nomogram proved to be a valuable tool for predicting PDH after eTSS for PAs and demonstrated good generalizability.Patients could benefit from early identification of PDH and optimized treatment decisions.

A cytoprotective graphene oxide-polyelectrolytes nanoshell for single-cell encapsulation

Graphene oxide(GO)has been increasingly utilized in the fields of food,biomedicine,environment and other fields because of its benign biocompatible.We encapsulated two kinds of GO with different sizes on yeast cells with the assistance of polyelectrolytes poly(styrene sulfonic acid)sodium salt(PSS)and polyglutamic acid(PGA)(termed as Y@GO).The result does not show a significant difference between the properties of the two types of Y@GO(namely Y@GO1 and Y@GO2).The encapsulation layers are optimized as Yeast/PGA/PSS/PGA/GO/PGA/PSS based on the morphology,dispersity,colony-forming unit,and zeta potential.The encapsulation of GO increases the roughness of the yeast.It is proved that the Y@GO increases the survival time and enhance the activity of yeast cells.The GO shell improves the resistance of yeast cells against pH and salt stresses and extends the storage time of yeast cells.