Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

Objective To evaluate the diagnostic value of cardiac magnetic resonance(CMR)in patients with severe connective tissue disease-associated pulmonary hypertension(CTD-PAH).Methods A total of 48 patients diagnosed with CTD-PAH by right heart catheterization(RHC)in Tianjin Medical University General Hospital from June 2018 to July 2021 were retrospectively included.The parameters of right ventricular(RV)morphology,function and ventricular septum(IVS)were obtained by manual delineation on CMR images and corrected by body surface area.The late gadolinium enhancement(LGE)myocardial mass(MM)and its percentage in left ventricular(LV)MM were manually sketched and calculated on LGE images.The patients were divided into the mild-moderate group and the severe group according to mean pulmonary arterial pressure(mPAP).CMR parameters were compared between the two groups.The diagnostic value of CMR for severe CTD-PAH was analyzed by receiver operating characteristic(ROC)curve.Results A total of 48 patients with CTD-PAH were included in this study.The curvature of interventricular septum(CIVS)and RV ejection fraction(EF)were lower in the severe group than those in the mild-moderate group,and the time proportion of IVS deformation,RV end-diastolic volume index(EDVI),RV end-systolic volume index(ESVI)and RV MM were higher than those in the mild-moderate group(P＜0.05).ROC curve analysis showed that RV MM,time proportion of IVS deformation and RV ESVI had better diagnostic efficacy in severe CTD-PAH patients(AUC was 0.792,0.766 and 0.731,respectively).The combined AUC of the three parameters was 0.840,specificity was 85.7%and sensitivity was 79.4%.Conclusion The parameters of RV and IVS measured by CMR can effectively evaluate patients with severe CTD-PAH and directly reflect serverity of cardiac impairment in patients with severe CTD-PAH from the morphological and functional perspective.

Objective To investigate the Fsp27 gene's influence on the regulation of hepatic stellate cells (HSCs) in vitro.Methods HSCs were isolated from rat liver,the Fsp27 gene was detected in primary HSCs,and activated HSCs were detected by RT-qPCR.After 72 h of Fsp27 transduction through a lentivirus expressing Fsp27 (pLV-Fsp27),the proliferation of HSCs was tested by the CCK-8 test kit,smooth muscle α-actin (α-SMA) expression of HSCs was tested by Western blot,and the fibrosis-related genes were tested by RT-qPCR.Results The HSCs were isolated and cultured successfully,and the Fsp27 genetic difference between primary and activated HSCs was significant (P＜0.01).After coculture for 72 h,Fsp27 inhibited the proliferation and activation of HSCs (P＜0.05).Fsp27 can enhance expression of the MMP-2 gene and down-regulate expression of the TIMP-1 and TGF-β1 gene in activated HSCs (P＜0.05).Conclusion The Fsp27 gene can inhibit the proliferation and activation of HSCs,regulate the expression of fibrosis-related genes,and may play an important role in maintaining the quiescent phenotype of HSCs.