ERp57 dysfunction has been shown to contribute to tumorigenesis in multiple malignances. However, the role of ERp57 in clear cell renal carcinoma (ccRCC) remains unclear. Cell proliferation ability was measured by MTT and colony forming assays. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to measure protein and mRNA expression. Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) were performed to detect protein-protein interaction. Chromatin immunoprecipitation (ChIP), ribonucleoprotein immunoprecipitation (RIP), and oligo pull-down were used to confirm DNA–protein and RNA–protein interactions. Promoter luciferase analysis was used to detect transcription factor activity. Here we found ERp57 was overexpressed in ccRCC tissues, and the higher levels of ERp57 were correlated with poor survival in patients with ccRCC. In vivo and in vitro experiments showed that ccRCC cell proliferation was enhanced by ERp57 overexpression and inhibited by ERp57 deletion. Importantly, we found ERp57 positively regulated ILF3 expression in ccRCC cells. Mechanically, ERp57 was shown to bind to STAT3 protein and enhance the STAT3-mediated transcriptional activity of ILF3. Furthermore, ILF3 levels were increased in ccRCC tissues and associated with poor prognosis. Interestingly, we revealed that ILF3 could bind to ERp57 and positively regulate its expression by enhancing its mRNA stability. Furthermore, ccRCC cell proliferation was moderated via the ERp57/STAT3/ILF3 feedback loop. In summary, our results indicate that the ERp57/STAT3/ILF3 feedback loop plays a key role in the oncogenesis of ccRCC and provides a potential therapeutic target for ccRCC treatment.

Background: Ischemia reperfusion injury (IRI) has been shown to increase the risk of tumor recurrence after liver surgery. Also, nonalcoholic fatty liver disease (NAFLD) is associated with increased HCC recurrence. ALOX12–12-HETE pathway is activated both in liver IRI and NASH. Also, ALOX12–12-HETE has been shown to mediate tumorigenesis and progression. Therefore, our study aims to investigate whether the ALOX12–12-HETE-GPR31 pathway involved in IRI induced HCC recurrence in NAFLD. Methods: HCC mouse model was used to mimic the HCC recurrence in NAFLD. Western Blot, qPCR, Elisa and Immunofluorescence analysis were conducted to evaluate the changes of multiple signaling pathways during HCC recurrence, including ALOX12–12-HETE axis, EMT, MMPs and PI3K/AKT/NF-κB signaling pathway. We also measured the expression and functional changes of GPR31 by siRNA. Results: ALOX12–12-HETE pathway was activated in liver IRI and its activation was further enhanced in NAFLD, which induced more severe HCC recurrence in fatty livers than normal livers. Inhibition of ALOX12–12-HETE by ML355 reduced the HCC recurrence in fatty livers. In vitro studies showed that 12-HETE increased the expression of GPR31 and induced epithelial-mesenchymal transition (EMT) and matrix metalloprotein (MMPs) by activating PI3K/AKT/NF-κB pathway. Furthermore, knockdown of GPR31 in cancer cells inhibited the HCC recurrence in NAFLD. Conclusions: ALOX12–12-HETE-GPR31 played an important role in HCC recurrence and might be a potential therapeutic target to reduce HCC recurrence after surgery in fatty livers.

Background: Disseminating disease knowledge through concise videos on various platforms is an innovative and efficient approach. However, it remains uncertain whether pancreatic neuroendocrine tumor (pNET)-related videos available on current short video platforms can effectively convey accurate and impactful information to the general public. Objective: Our study aims to extensively analyze the quality of pNET-related videos on TikTok and Bilibili, intending to enhance the development of pNET-related social media content to provide the general public with more comprehensive and suitable avenues for accessing pNET-related information. Methods: A total of 168 qualifying videos pertaining to pNETs were evaluated from the video-sharing platforms Bilibili and TikTok. Initially, the fundamental information conveyed in the videos was documented. Subsequently, we discerned the source and content type of each video. Following that, the Global Quality Scale (GQS) and modified DISCERN (mDISCERN) scale were employed to appraise the educational value and quality of each video. A comparative evaluation was conducted on the videos obtained from these two platforms. Results: The number of pNET-related videos saw a significant increase since 2020, with 9 videos in 2020, 19 videos in 2021, 29 videos in 2022, and 106 videos in 2023. There were no significant improvements in the mean GQS or mDISCERN scores from 2020 to 2023, which were 3.22 and 3.00 in 2020, 3.33 and 2.94 in 2021, 2.83 and 2.79 in 2022, and 2.78 and 2.94 in 2023, respectively. The average quality scores of the videos on Bilibili and Tiktok were comparable, with GQS and mDISCERN scores of 2.98 on Bilibili versus 2.77 on TikTok and 2.82 on Bilibili versus 3.05 on TikTok, respectively. The source and format of the videos remained independent factors affecting the two quality scores. Videos that were uploaded by professionals (hazard ratio=7.02, P=.002) and recorded in specialized popular science formats (hazard ratio=12.45, P<.001) tended to exhibit superior quality. Conclusions: This study demonstrates that the number of short videos on pNETs has increased in recent years, but video quality has not improved significantly. This comprehensive analysis shows that the source and format of videos are independent factors affecting video quality, which provides potential measures for improving the quality of short videos.

PARP-1 promotes tumor recurrence after warm ischemic liver graft transplantation via neutrophil recruitment and polarization PARP-1 promotes tumor recurrence after warm ischemic liver graft transplantation via neutrophil recruitment and polarization

The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.